Marek Romanowski

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Scholarly Contributions

Chapters

• Leung, S., & Romanowski, M. (2014). Biomedical Applications: Composite Nanocapsules, Dielectric Properties. In Dekker Encyclopedia of Nanoscience and Nanotechnology, Third Edition(pp pp. 336–346). CRC Press.
• Parker, W., Romanowski, M., & Song, P. (1991). Conformation and its functional implications in phytochrome. In Phytochrome Properties and Biological Action(pp pp. 85-112). Springer.

Journals/Publications

• Chambers, R., Quon, N., Slomka, B., Martirosyan, N., Lemole, M., & Romanowski, M. (2020). Pupillary sensor for ocular cranial nerve monitoring. Proc. SPIE 11225, Clinical and Translational Neurophotonics, XV, 1125510. doi:10.1117/12.2542058
• Romanowski, M., Dawson, P., & Nguyen, V. (2020). Spectral engineering of UV luminescence of upconverting nanoparticles. Proc. SPIE 11255, Colloidal Nanoparticles for Biomedical Applications, XV, 1125510. doi:10.1117/12.2546826
• Dawson, P., & Romanowski, M. (2018). Excitation Modulation of Upconversion Nanoparticles for Switch-like Control of Ultraviolet Luminescence. Journal of the American Chemical Society, 140, 5714-5718.
• Knights-Mitchell, S., & Romanowski, M. (2018). Near-Infrared Activated Release Of Doxorubicin From Plasmon Resonant Liposome. Nanotheranostics, 2, 295-305.
• Watson, J. R., Martirosyan, N., Lemole, G. M., Trouard, T. P., & Romanowski, M. (2018). Intraoperative brain tumor resection with indocyanine green using augmented microscopy. Journal of Biomedcial Optics, 23, 090501.
• Watson, J., Garland, S., & Romanowski, M. (2017). Intraoperative Visualization of Plasmon Resonant Liposomes Using Augmented Microscopy. Molecular-Guided Surgery: Molecules, Devices, and Applications III.
• Watson, J. R., Martirosyan, N. L., Garland, S., Lemole, G. M., & Romanowski, M. (2016). Intraoperative Imaging using Intravascular Contrast Agent Proc SPIE9696. Molecular-Guided Surgery: Molecules, Devices, and Applications II, Proc SPIE 142296960L. doi:10.1117/12.2213867
• Watson, J., Martirosyan, N., Garland, S., Lemole, G. M., & Romanowski, M. (2016). Intraoperative imaging using intravascular contrast agents. Progress in Biomedical optics and Imaging - Proceedings of SPIE, 9696, 96960L.
• Knights-Mitchell, S. S., & Romanowski, M. (2015). Plasmon resonant liposomes for controlled drug delivery. Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 9338.
• Martirosyan, N. L., Skoch, J., Watson, J. R., Lemole, G. M., Romanowski, M., & Anton, R. (2015). Integration of indocyanine green videoangiography with operative microscope: augmented reality for interactive assessment of vascular structures and blood flow. Neurosurgery, 11 Suppl 2, 252-7; discussion 257-8.
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  Preservation of adequate blood flow and exclusion of flow from lesions are key concepts of vascular neurosurgery. Indocyanine green (ICG) fluorescence videoangiography is now widely used for the intraoperative assessment of vessel patency.
• Watson, J. R., Gainer, C. F., Martirosyan, N., Skoch, J., Lemole, G. M., Anton, R., & Romanowski, M. (2015). Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images. Journal of Biomedical Optics, 20(10), 106002.
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  Intraoperative applications of near-infrared (NIR) fluorescent contrast agents can be aided by instrumentation capable of merging the view of surgical field with that of NIR fluorescence. We demonstrate augmented microscopy, an intraoperative imaging technique in which bright-field (real) and electronically processed NIR fluorescence (synthetic) images are merged within the optical path of a stereomicroscope. Under luminance of 100,000 lx, representing typical illumination of the surgical field, the augmented microscope detects 189 nM concentration of indocyanine green and produces a composite of the real and synthetic images within the eyepiece of the microscope at 20 fps. Augmentation described here can be implemented as an add-on module to visualize NIR contrast agents, laser beams, or various types of electronic data within the surgical microscopes commonly used in neurosurgical, cerebrovascular, otolaryngological, and ophthalmic procedures.
• Watson, J. R., Martirosyan, N., Skoch, J., Lemole, G. M., Anton, R., & Romanowski, M. (2015). Augmented microscopy with near-infrared fluorescence detection. Progress in Biomedical Optics and Imaging - Proceeedings of SPIE, 9311.
• Watson, J. R., Martirosyan, N., Skoch, J., Lemole, G. M., Anton, R., & Romanowski, M. (2015). Augmented microscopy with near-infrared fluorescence detection. Proc. SPIE. 9311. Molecular-Guided Surgery: Molecules, Devices, and Applications, 93110I. doi:10.1117/12.2077008
• Gainer, C. F., & Romanowski, M. (2014). A review of synthetic methods for the production of upconverting lanthanide nanoparticles. Journal of Innovative Optical Health Sciences, 1330007.
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  Abstract: Upconverting lanthanide nanoparticles overcome many of the problems associated with more traditionally used luminescent contrast agents, such as photobleaching, autofluorescence, cytotoxicity and phototoxicity. For this reason, they are an attractive choice for biomedical imaging applications, particularly for imaging in living tissues. The last decade has seen numerous improvements to these nanocrystals, but a comprehensive guide to the synthesis of upconverting lanthanide nanoparticles has not yet been written. Methods vary from paper to paper and from group to group, and results vary between research groups for each method. For this reason, development of these nanoparticles remains a significant endeavor for any research group interested in joining the field. In this review, we look at the varying synthetic methods employed over the last decade and detail methodology for a select few that have been favored in the field. © 2014 The Authors.
• Knights-Mitchell, S., & Romanowski, M. (2014). Modification of Commercial Liposomal Drug Carrier by Plasmon Resonant Coating. Technical Proceedings of the 2014 NSTI Nanotechnology Conference and Expo, 2, 311-314.
• Orsinger, G. V., Watson, J. M., Gordon, M., Nymeyer, A. C., de Leon, E. E., Brownlee, J. W., Hatch, K. D., Chambers, S. K., Barton, J. K., Kostuk, R. K., & Romanowski, M. (2014). Simultaneous multiplane imaging of human ovarian cancer by volume holographic imaging. Journal of Biomedical Optics, 19(3), 36020.
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  Ovarian cancer is the most deadly gynecologic cancer, a fact which is attributable to poor early detection and survival once the disease has reached advanced stages. Intraoperative laparoscopic volume holographic imaging has the potential to provide simultaneous visualization of surface and subsurface structures in ovarian tissues for improved assessment of developing ovarian cancer. In this ex vivo ovarian tissue study, we assembled a benchtop volume holographic imaging system (VHIS) to characterize the microarchitecture of 78 normal and 40 abnormal tissue specimens derived from ovarian, fallopian tube, uterine, and peritoneal tissues, collected from 26 patients aged 22 to 73 undergoing bilateral salpingo-oophorectomy, hysterectomy with bilateral salpingo-oophorectomy, or abdominal cytoreductive surgery. All tissues were successfully imaged with the VHIS in both reflectance- and fluorescence-modes revealing morphological features which can be used to distinguish between normal, benign abnormalities, and cancerous tissues. We present the development and successful application of VHIS for imaging human ovarian tissue. Comparison of VHIS images with corresponding histopathology allowed for qualitatively distinguishing microstructural features unique to the studied tissue type and disease state. These results motivate the development of a laparoscopic VHIS for evaluating the surface and subsurface morphological alterations in ovarian cancer pathogenesis.
• Orsinger, G. V., Williams, J. D., & Romanowski, M. (2014). Focal activation of cells by plasmon resonance assisted optical injection of signaling molecules. ACS Nano, 8(6), 6151-62.
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  Experimental methods for single cell intracellular delivery are essential for probing cell signaling dynamics within complex cellular networks, such as those making up the tumor microenvironment. Here, we show a quantitative and general method of interrogation of signaling pathways. We applied highly focused near-infrared laser light to optically inject gold-coated liposomes encapsulating bioactive molecules into single cells for focal activation of cell signaling. For this demonstration, we encapsulated either inositol trisphosphate (IP3), an endogenous cell signaling second messenger, or adenophostin A (AdA), a potent analogue of IP, within 100 nm gold-coated liposomes, and injected these gold-coated liposomes and their contents into the cytosol of single ovarian carcinoma cells to initiate calcium (Ca(2+)) release from intracellular stores. Upon optical injection of IP3 or AdA at doses above the activation threshold, we observed increases in cytosolic Ca(2+) concentration within the injected cell initiating the propagation of a Ca(2+) wave throughout nearby cells. As confirmed by octanol-induced inhibition, the intercellular Ca(2+) wave traveled via gap junctions. Optical injection of gold-coated liposomes represents a quantitative method of focal activation of signaling cascades of broad interest in biomedical research.
• Romanowski, M., Orsinger, G., & Williams, J. (2014). Intracellular light-induced release of signaling molecules from gold-coated liposomes. Progress in Biomedical Optics and Imaging - Proceedings of SPIE, IX, 89551G.
• Gainer, C. F., & Romanowski, M. (2013). Multiphoton imaging of upconverting lanthanide nanoparticles in three dimensional models of cancer. Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8595.
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  Abstract: While upconverting lanthanide nanoparticles have numerous advantages over other exogenous contrast agents used in scanned multiphoton imaging, their long luminescence lifetimes cause images collected with non-descanned detection to be greatly blurred. We demonstrate herein the use of Richardson-Lucy deconvolution to deblur luminescence images obtained via multiphoton scanning microscopy. Images were taken of three dimensional models of colon and ovarian cancer following incubation with NaYF4:Yb,Er nanoparticles functionalized with an antibody for EGFR and folic acid respectively. Following deconvolution, images had a lateral resolution on par with the optimal performance of the imaging system used, ∼1.2 μm, and an axial resolution of ∼5 μm. Due to the relatively high multiphoton excitation efficiency of these nanoparticles, it is possible to follow binding of individual particles in tissue. In addition, their extreme photostability allows for prolonged imaging without significant loss in luminescence signal. With these advantageous properties in mind, we also discuss the potential application of upconverting lanthanide nanoparticles for tracking of specific, cancer relevant receptors in tissue. © 2013 Copyright SPIE.
• Orsinger, G. V., & Romanowski, M. (2013). Gold-coated liposomes encapsulating signaling molecules for initiating cellular communication. Technical Proceedings of the 2013 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2013, 3, 270-273.
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  Abstract: Cell signaling in the tumor microenvironment is critical for the initiation, progression and metastasis of cancer. To better understand these communication pathways and therefore better design and develop therapies and diagnostics for cancers, experimental methods of probing cellular communication at a single to multi-cell level are needed. Here, we manipulate gold-coated liposomes encapsulating signaling molecules using an optical trap to initate cell signling cascades. The high polarizability of the liposome's unique gold shell allows stable optical trapping for subcellular manipulation in the presence of cells. Specifically, we encapsulated the cell signaling molecule inositol trisphosphate (IP3), a ubiquitous intracellular secondary messenger involved in GPCR and Akt signaling cascades, within 100 nm gold-coated liposomes and used an optical trapping laser to deliver liposomes into the cytosol of a single cell to initiate localized cell signaling. Upon optical injection of liposomal IP3 into a single ovarian carcinoma cell, we observed localized activation as reported by changes in Indo-1 fluorescence intensity. With established gap junctions between the injected cell and neighboring cells, we monitored propagation of this signaling to and through nearby cells. Subsequently, we investigated the ability to modulate cell signaling by, for example, varying the number of lP3-containing gold-coated liposomes injected into a single cell. By combining optical trapping with gold-coated liposomes encapsulating signaling molecules, we present a unique in vitro tool for studying cell signaling within the tumor microenvironment.
• Orsinger, G. V., Leung, S. J., & Romanowski, M. (2013). Activation of cell signaling via optical manipulation of gold-coated liposomes encapsulating signaling molecules. Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8587.
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  Abstract: Many diseases involve changes in cell signaling cascades, as seen commonly in drug resistant cancers. To better understand these intricate signaling events in diseased cells and tissues, experimental methods of probing cellular communication at a single to multi-cell level are required. We recently introduced a general platform for activation of selected signaling pathways by optically controlled delivery and release of water soluble factors using gold-coated liposomes. In the example presented here, we encapsulated inositol trisphosphate (IP3), a ubiquitous intracellular secondary messenger involved in GPCR and Akt signaling cascades, within 100 nm gold-coated liposomes. The high polarizability of the liposome's unique gold pseudo-shell allows stable optical trapping for subcellular manipulation in the presence of cells. We take this optical manipulation further by optically injecting IP3-containing liposomes into the cytosol of a single cell to initiate localized cell signaling. Upon optical injection of liposomal IP3 into a single ovarian carcinoma cell, we observed localized activation as reported by changes in Indo-1 fluorescence intensity. With established gap junctions between the injected cell and neighboring cells, we monitored propagation of this signaling to and through nearby cells. © 2013 Copyright SPIE.
• Romanowski, M., Romanowski, M. -., Black, K. C., Kirkpatrick, N. D., Troutman, T. S., Xu, L., Vagner, J., Gillies, R. J., Barton, J. K., & Utzinger, U. (2008). Gold nanorods targeted to delta opioid receptor: plasmon-resonant contrast and photothermal agents. Molecular Imaging, 7(1).
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  Molecularly targeted gold nanorods were investigated for applications in both diagnostic imaging and disease treatment with cellular resolution. The nanorods were tested in two genetically engineered cell lines derived from the human colon carcinoma HCT-116, a model for studying ligand-receptor interactions. One of these lines was modified to express delta opioid receptor (deltaOR) and green fluorescent protein, whereas the other was receptor free and expressed a red fluorescent protein, to serve as the control. Deltorphin, a high-affinity ligand for deltaOR, was stably attached to the gold nanorods through a thiol-terminated linker. In a mixed population of cells, we demonstrated selective imaging and destruction of receptor-expressing cells while sparing those cells that did not express the receptor. The molecularly targeted nanorods can be used as an in vitro ligand-binding and cytotoxic treatment assay platform and could potentially be applied in vivo for diagnostic and therapeutic purposes with endoscopic technology.
• Gainer, C. F., Joshua, G. S., & Romanowski, M. (2012). Toward the Use of Two-Color Emission Control in Upconverting NaYF4:Er(3+), Yb(3+) Nanoparticles for Biomedical Imaging. Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8231.
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  In the interest of generating new biomedical sensing techniques as well as improving those that currently exist, a great deal of attention has been given to upconverting lanthanide nanoparticles in recent years. In order to develop these nanoparticles for use in multiplexed and ratiometric sensing techniques, many recent studies have focused on experimental control of their emission wavelengths. Here we describe a new method for controlling the relative intensity of green and red emission bands in NaYF4:Yb(3+), Er(3+) nanoparticles via control of the excitation pulse repetition rate. Using this method, particles of the same composition may be tuned to produce red and green light in user-defined ratios. We discuss the mechanism behind this control as well as potential applications that could make use of this property, specifically in super resolution imaging techniques.
• Leung, S. J., & Romanowski, M. (2012). Light-activated content release from liposomes. Theranostics, 2(10), 1020-36.
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  Successful integration of diagnostic and therapeutic actions at the level of individual cells requires new materials that combine biological compatibility with functional versatility. This review focuses on the development of liposome-based functional materials, where payload release is activated by light. Methods of sensitizing liposomes to light have progressed from the use of organic molecular moieties to the use of metallic plasmon resonant structures. This development has facilitated application of near infrared light for activation, which is preferred for its deep penetration and low phototoxicity in biological tissues. Presented mechanisms of light-activated liposomal content release enable precise in vitro manipulation of minute amounts of reagents, but their use in clinical diagnostic and therapeutic applications will require demonstration of safety and efficacy.
• Leung, S. J., & Romanowski, M. (2012). Molecular catch and release: controlled delivery using optical trapping with light-responsive liposomes. Advanced Materials, 24(47), 6380-3.
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  Gold-coated liposomes are maneuvered using an optical trap to achieve precise delivery of encapsulated molecular cargo. Movement and payload release from these plasmon resonant nanocapsules are independently controlled using a pulsed trapping beam. This technology enables in vitro delivery of a payload to a selected cell and may be applied to the interrogation of individual cells within their biological microenvironment.
• Leung, S. J., & Romanowski, M. (2012). NIR-activated content release from plasmon resonant liposomes for probing single-cell responses. ACS Nano, 6(11), 9383-91.
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  Technological limitations have prevented the interrogation and manipulation of cellular activity in response to bioactive molecules within model and living systems that is required for the development of diagnostic and treatment modalities for diseases, such as cancer. In this work, we demonstrate that gold-coated liposomes are capable of encapsulation and on-demand release of signaling molecules with a spatial and temporal resolution leading to activation of individual cells. As a model system, we used cells modified to overexpress a certain G-protein coupled receptor, the CCK2 receptor, and achieved its activation in a single cell via the localized release of its agonist. This content release was triggered by illumination of the liposomes at wavelengths corresponding to the plasmon resonance of the gold coating. The use of plasmon resonant liposomes may enable on-demand release of a broad range of molecules using biologically safe near-infrared light and without molecule chemical modification. In combination with the spectral tunability of plasmon resonant coating, this technology may allow for multiplexed interrogation of complex and diverse signaling pathways in model or living tissues with unprecedented spatial and temporal control.
• Leung, S. J., & Romanowski, M. (2012). Optical trapping of gold-coated liposomes. Technical Proceedings of the 2012 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2012, 648-651.
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  Abstract: To address unmet needs in the area of controlled delivery, we introduced a nanocomposite material, plasmon resonant gold-coated liposomes. We previously showed that gold-coated liposomes display plasmon resonance that is tunable in the near-infrared range and are capable of light-induced content release. The plasmon resonant structure facilitates rapid content release when illuminated with laser light at wavelengths that correspond to the spectral position of the resonance band. Here, we demonstrate optical trapping of gold-coated liposomes that allows for controlled movement of these liposomes within a biological sample. Furthermore, we computationally refined this experimental system with the potential for delivery and localized release of an encapsulated agent with high spatial and temporal resolution. Full development of this technology will enable accurate perturbation of cellular functions in response to released compounds, with applications in signaling pathway research and drug discovery.
• Leung, S. J., & Romanowski, M. (2012). Single cell targeting using plasmon resonant gold-coated liposomes. Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 8234.
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  Abstract: We have developed an experimental system with the potential for the delivery and localized release of an encapsulated agent with high spatial and temporal resolution. We previously introduced liposome-supported plasmon resonant gold nanoshells; in this composite structure, the liposome allows for the encapsulation of substances, such as therapeutic agents, neurotransmitters, or growth factors, and the plasmon resonant structure facilitates the rapid release of encapsulated contents upon laser light illumination. More recently, we demonstrated that these gold-coated liposomes are capable of releasing their contents in a spectrally-controlled manner, where plasmon resonant nanoparticles only release content upon illumination with a wavelength of light matching their plasmon resonance band. We now show that this release mechanism can be used in a biological setting to deliver a peptide derivative of cholecystokinin to HEK293 cells overexpressing the CCK2 receptor. Using directed laser light, we may enable localized release from gold-coated liposomes to enable accurate perturbation of cellular functions in response to released compounds; this system may have possible applications in signaling pathways and drug discovery. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).
• Orsinger, G. V., Leung, S. J., Knights-Mitchell, S., Williams, J. D., & Romanowski, M. (2012). Drug delivery with light-activated gold-coated liposomes. Technical Proceedings of the 2012 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2012, 134-137.
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  Abstract: With the ultimate goal of delivering therapeutic compounds selectively to cancerous or diseased tissues and cells, we have presented liposome-based plasmon resonant nanocapsules. The liposome's lipid membrane allows for encapsulation of a small volume of soluble therapeutic or diagnostic compounds, while the surrounding plasmon resonant gold structure elicits rapid release of the liposomes' contents when illuminated by laser light at wavelengths corresponding to the spectral position of the plasmon resonance band. By depositing discrete gold nanoclusters onto the surface of 100 nm diameter thermosensitive liposomes, we harness the plasmon resonance of a gold pseudo-shell while maintaining degradability to a size compatible with renal clearance. In this work we describe optimization of the liposome design which combines stable encapsulation at physiological temperatures and gold coating responsive at near infrared wavelengths. The described biocompatible composite delivery vehicle enables encapsulation and selective release of therapeutic or contrast agents upon application of a light stimulus for applications in biomedical imaging, diagnostics, therapeutics and targeted drug delivery.
• Romanowski, M., Romanowski, M. -., Gainer, C. F., & Utzinger, U. (2012). Scanning two-photon microscopy with upconverting lanthanide nanoparticles via Richardson-Lucy deconvolution. Journal of Biomedical Optics, 17(7).
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  The use of upconverting lanthanide nanoparticles in fast-scanning microscopy is hindered by a long luminescence decay time, which greatly blurs images acquired in a nondescanned mode. We demonstrate herein an image processing method based on Richardson-Lucy deconvolution that mitigates the detrimental effects of their luminescence lifetime. This technique generates images with lateral resolution on par with the system's performance, ∼1.2  μm, while maintaining an axial resolution of 5 μm or better at a scan rate comparable with traditional two-photon microscopy. Remarkably, this can be accomplished with near infrared excitation power densities of 850 W/cm(2), several orders of magnitude below those used in two-photon imaging with molecular fluorophores. By way of illustration, we introduce the use of lipids to coat and functionalize these nanoparticles, rendering them water dispersible and readily conjugated to biologically relevant ligands, in this case epidermal growth factor receptor antibody. This deconvolution technique combined with the functionalized nanoparticles will enable three-dimensional functional tissue imaging at exceptionally low excitation power densities.
• Leung, S. J., Kachur, X. M., Bobnick, M. C., & Romanowski, M. (2011). Wavelength-selective light-induced release from plasmon resonant liposomes. Advanced Functional Materials, 21(6), 1113-1121.
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  Abstract: Biodegradable, spectrally tunable plasmon resonant nanocapsules are created via the deposition of gold onto the surface of 100 nm diameter thermosensitive liposomes. These nanocapsules exhibit selective release of encapsulated contents upon illumination with light of a wavelength matching their distinct resonance bands. In this study, 760 and 1210 nm laser illumination elicits complete release from gold-coated liposomes with a corresponding resonance, while causing minimal release from liposomes with an unmatching resonance. Spectrally selective release is accomplished through the use of multiple, low-intensity laser pulses delivered over a period of minutes, ensuring that illumination affects the gold-coated liposomes without heating the surrounding media. The use of pulsed illumination to achieve spectral selectivity is validated experimentally and through modeling of the heat equation. The result of this illumination scheme for selective release using multiple wavelengths of light is a biologically safe mechanism for realizing drug delivery, microfluidic, and sensor applications. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
• Leung, S., & Romanowski, M. (2011). Light-induced release from gold-coated liposomes. Technical Proceedings of the 2011 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2011, 3, 295-297.
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  Abstract: We have computationally refined an experimental system with the potential for delivery and localized release of an encapsulated agent with high spatial and temporal resolution. We recently presented liposome-supported plasmon resonant gold nanoshells; in this composite structure, the liposome allows for the encapsulation of substances and the plasmon resonant structure facilitates rapid release of encapsulated contents upon laser light illumination. Using computational modeling, we now demonstrate that these liposome-supported nanoshells induce less local heating than solid gold spheres under optical trapping conditions, reducing their likelihood of damaging biological tissues used with this manipulation mechanism. We then present a general scheme for trapping of and localized release from gold-coated liposomes to enable accurate perturbation of cellular functions in response to released compounds, with possible applications in signalling pathways and drug discovery.
• Romanowski, M., Gainer, C. F., Joshua, G. S., De Silva, C. R., & Romanowski, M. -. (2011). Control of Green and Red Upconversion in NaYF4:Yb(3+),Er(3+) Nanoparticles by Excitation Modulation. Journal of materials chemistry, 21(46).
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  Control of the two strongest upconversion emission lines in NaYF4:Yb(3+), Er(3+) nanoparticles is demonstrated by varying the excitation repetition rate. This technique may enable new multiplexed sensing modalities based on multicolor luminescent nanoparticles, currently contemplated for biomedical imaging and diagnostics.
• Leung, S. J., Bobnick, M. C., & Romanowski, M. (2010). Plasmon resonant gold-coated liposomes for spectrally controlled content release. Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 7577.
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  Abstract: We recently demonstrated that liposome-supported plasmon resonant gold nanoshells are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). When illuminated with laser light at the wavelength matching their plasmon resonance band, gold-coated liposomes rapidly release their encapsulated substances, which can include therapeutic and diagnostic agents. The present research demonstrates that release of encapsulated agents from gold-coated liposomes can be spectrally controlled by varying the location of the plasmon resonance band; this spectral tuning is accomplished by varying the concentration of gold deposited on the surface of liposomes. Furthermore, the amount of laser energy required for release is qualitatively explained using the concept of thermal confinement (Jacques, Appl. Opt. 1993, 32(3), 2447-2454). Overlapping thermal confinement zones can be avoided by minimizing the laser pulse width, resulting in lower energy requirements for liposomal content release and less global heating of the sample. Control of heating is especially important in drug delivery applications, where it enables spatial and spectral control of delivery and prevents thermal damage to tissue. © 2010 Copyright SPIE - The International Society for Optical Engineering.
• Troutman, T. S., Leung, S. J., & Romanowski, M. (2009). Light-induced content release from plasmon-resonant liposomes. Advanced Materials, 21(22), 2334-2338.
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  Abstract: A study was conducted to demonstrate light-induced content release from plasmon-resnant liposomes. The study also involved encapsulation of a model compound in thermosenstive liposomes, which then coated with gold to form plasmon-resonant shells with optical resonance tunable in the near-infrared range. It was observed that when exposed to 1064 nm laser light, these liposomes released their content in a spectrally-dependent manner. It was also found that the plasmon-resonant coating deposited on the surface of temperature-sensitive liposomes enhanced light-controlled release of payloads through the photothermal conversion of energy of absorbed light. The reduction of gold to the surface of the liposomes produced a final structure of 127 nm in diameter. This method could be used for application in complex diagnostic tests and therapeutic intervention requiring sequential delivery of agents.
• Troutman, T. S., Barton, J. K., & Romanowski, M. (2008). Biodegradable plasmon resonant nanoshells. Advanced Materials, 20(13), 2604-2608.
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  Abstract: A study has illustrated the preparation and testing of biodegradable plasmon resonant nanoshells of 63 nm diameter formed using shell sprayed array of gold clusters supported on a spherical biodegradable core. The proposed grade of materials maintains optical tunability characteristics of solid metallic shells, and upon degradation yields individual clusters of 5.7 nm diameter, compatible with requirements of renal clearance. The attempt on biodegradable metallic nanoparticles may enable clinical translation of many research stage technologies. The study has prepared degradable plasmon resonant nanostructures, in which liposomes made of dialkyl phosphatidylcholine served as the spherical template, and also developed the composite shell obtained by formation of gold-lipid complexes. Biodegradable plasmon resonant contrast agents may improve clinical OCT images, and can also further enhance in vivo targeting and detection of molecular markers of diagnostic importance.
• Romanowski, M., Romanowski, M. -., Troutman, T. S., & Barton, J. K. (2007). Optical coherence tomography with plasmon resonant nanorods of gold. Optics Letters, 32(11).
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  We explored plasmon resonant nanorods of gold as a contrast agent for optical coherence tomography (OCT). Nanorod suspensions were generated through wet chemical synthesis and characterized with spectrophotometry, transmission electron microscopy, and OCT. Polyacrylamide-based phantoms were generated with appropriate scattering and anisotropy coefficients (30 cm(-1) and 0.89, respectively) to image distribution of the contrast agent in an environment similar to that of tissue. The observed signal was dependent on whether the plasmon resonance peak overlapped the source bandwidth of the OCT, confirming the resonant character of enhancement. Gold nanorods with plasmon resonance wavelengths overlapping the OCT source yielded a signal-to-background ratio of 4.5 dB, relative to the tissue phantom. Strategies for OCT imaging with nanorods are discussed.
• Williams, J., Lansdown, R., Sweitzer, R., Romanowski, M., LaBell, R., Ramaswami, R., & Unger, E. (2003). Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors. Journal of Controlled Release, 91(1-2), 167-172.
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  PMID: 12932648;Abstract: Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar® in a mouse xenograft tumor model. © 2003 Elsevier B.V. All rights reserved.
• Romanowski, M., Zhu, X., Kim, K., Hruby, V. J., & O'Brien, D. F. (2002). Interaction of enkephalin peptides with anionic model membranes. Biochimica et Biophysica Acta - Biomembranes, 1558(1), 45-53.
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  PMID: 11750263;Abstract: According to the model for passive transport across the membranes, the total flow of permeant molecules is related to the product of the water-membrane partition coefficient and the diffusion coefficient, and to the water-membrane interfacial barrier. The effect of membrane surface charge on the permeability and interaction of analgesic peptide ligands with model membranes was investigated. A mixture of zwitterionic phospholipids with cholesterol was used as a model membrane. The lipid membrane charge density was controlled by the addition of anionic 1-palmitoyl-2-oleoylphosphatidylserine. Two classes of highly potent analgesic peptides were studied, c[D-Pen2,D-Pen5]enkephalin (DPDPE) and biphalin, a dimeric analog of enkephalin. The effect of increased surface charge on the permeability of the zwitterionic DPDPE is a relatively modest decrease, that appears to be due to a diminished partition coefficient. On the other hand the binding of the dicationic biphalin ligands to membranes increases proportionally with increased negative surface charge. This effect translates into a significant reduction of biphalin permeability by reducing the diffusion of the peptide across the bilayer. These experiments show the importance of electrostatic effects on the peptide-membrane interactions and suggest that the negative charge naturally present in cell membranes may hamper the membrane transport of some peptide drugs, especially cationic ones, unless there are cationic transporters present. © 2002 Elsevier Science B.V. All rights reserved.
• Guigen, L. i., Haq, W., Xiang, L., Lou, B., Hughes, R., A., I., Davis, P., Gillespie, T. J., Romanowski, M., Xiaoyun, Z., Misicka, A., Lipkowski, A. W., Porreca, F., Davis, T. P., Yamamura, H. I., O'Brien, D. F., & Hruby, V. J. (1998). Modifications op the 4,4'-residues and SAR studies of Biphalin, a highly potent opioid receptor active peptide. Bioorganic and Medicinal Chemistry Letters, 8(5), 555-560.
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  PMID: 9871617;Abstract: Modifications of 4,4' residues of Biphalin have resulted in greater binding selectivity and biological potency for the μ opioid receptor. A higher partition coefficient across the phospholipid bilayer membrane has been achieved by using a β-branched unusual amino acids.
• Romanowski, M., Zhu, X., Ramaswami, V., Misicka, A., Lipkowski, A. W., Hruby, V. J., & O'Brien, D. F. (1997). Interaction of a highly potent dimeric enkephalin analog, biphalin, with model membranes. Biochimica et Biophysica Acta - Biomembranes, 1329(2), 245-258.
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  PMID: 9371416;Abstract: Biphalin, (Tyr-D-Ala-Gly-Phe-NH)2, is a highly potent dimeric analog of enkephalin. Its analgesic efficacy is due in Dart to its ability to permeate the blood-brain barrier. To aid in understanding the mechanism of the transmembrane movement we determined and analyzed the permeability and partition coefficients of biphalin and a series of analogues where F, Cl, I, NO2, or NH2 were placed in the para position of the aromatic rings of Phe4,4'. Liposomes composed of neutral phospholipids and cholesterol were used as the model membrane. The overall good correlation between permeability and water-membrane partition coefficients suggests that the movement of biphalins across the model membrane is controlled by diffusion and depends on the water-membrane partition coefficient. To explain the observed correlation between permeability and the electron withdrawing/donating character of the substituents in the phenylalanine ring, we examined various folding patterns of Leu-enkephalin, an endogenous pentapeptide that exhibits affinities toward the same classes of opioid receptors (δ and μ). The observed permeabilities and partition coefficients of biphalin and analogues, as well as the tyrosine side chain accessibility, are consistent with the presence of the type of folding where the tyrosine and phenylalanine side chains are in a close contact. We propose that the aromatic ring interaction can promote the peptide permeability by stabilizing a more compact structure of biphalin that would minimize the number of hydrogen bonds with water and therefore enhances partitioning into the model membrane.
• Ramaswami, V., Zhu, X., Romanowski, M., Haaseth, R. C., Misicka, A., Lipkowski, A. W., Hruby, V. J., & O'Brien, D. F. (1996). Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides. International journal of peptide and protein research, 48(1), 87-94.
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  Permeability coefficients of a series of analogues of a potent opioid peptide, c[D-Pen2, D-Pen5]enkephalin, were measured in a model membrane system. The analogues included hydrophobic amino acid substitutions on position 3. Liposomes of a mixed composition consisting of zwitterionic lipids and cholesterol served as the model membranes. The obtained permeability coefficients range between 0.38 x 10(-12) and 2.9 x 10(-12) cm/s. These data were correlated with the hydrophobicity scale of Nozaki and Tanford (J. Biol. Chem. 246, 1971, 2211-2217) (correlation coefficient = 0.9933) and with determinations of lipid order perturbation by differential scanning calorimetry (correlation coefficient = -0.9779). The reasonably good correlation obtained within the family of analogues substituted on position 3 (Gly, Ala, Leu, Phe) indicates that changes in permeabilities are primarily related to increases in the partition coefficient of the peptide. However, Phe residue added on the N-terminal end of the peptide (position 0) does not appear to follow the observed trend, showing stronger lipid perturbation and lower permeability compared to the Phe3 analog. This observation demonstrates that each class of peptide modifications requires a new basis of permeability analysis and predictions.
• Romanowski, M., & Song, P. S. (1992). Structural domains of phytochrome deduced from homologies in amino acid sequences. Journal of protein chemistry, 11(2), 139-55.
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  A method of semiempirical identification of structural domains is proposed. The procedure is based on the comparison of amino acid sequences in groups of homologous proteins. This approach was tested using 32 known protein sequences from different cytochrome b5, cytochrome c, lysozyme, hemoglobin, and myoglobin proteins. The method presented was able to identify all structural domains of these reference proteins. A consensus secondary structure provided information on structural content of these domains predicting correctly 21 of 23 (91%) of alpha-helices. We applied this method to six homologous phytochrome sequences from Avena, Arabadopsis, Cucurbita, Maize, Oryza, and Pisum. Some of the identified domains can be assigned to the known tertiary structure categories. For example, an alpha/beta domain is localized in the region known to stabilize the phytochrome chromophore in the red light absorbing form (Pr). One alpha-helical and one alpha/beta domains are localized in regions important for the chromophore stabilization in the far-red absorbing form (Pfr). From an analysis of noncovalent interaction patterns in another domain it is proposed that a phytochrome dimer contact involves two segments localized between residues 730 and 821 (using numbering of aligned sequences). Also, a possible antiparallel beta-sheet structure of this region has been suggested. According to this model, the long axis of the interacting structures is perpendicular to a twofold symmetry axis of the phytochrome dimer.
• FRACKOWIAK, D., GRUDA, ., NIEDBALSKA, M., ROMANOWSKI, M., & DUDKOWIAK, A. (1991). POLARIZED ABSORPTION AND EMISSION-SPECTRA OF STILBAZOLIUM MEROCYANINES. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY, 54(1), 37-48.
• DRABENT, R., ROMANOWSKI, M., & FRACKOWIAK, D. (1990). SPECTRAL INVESTIGATIONS OF THE PHOTOREACTIONS OF FLAVOMONONUCLEOTIDE (FMN) IMMOBILIZED IN POLYMER FILM. SPECTROSCOPY LETTERS, 21(7), 495-508.
• FRACKOWIAK, D., FUJITA, Y., EROKHINA, L., MIMURO, M., YAMAZAKI, Y., TAMAI, N., NIEDBALSKA, M., ROMANOWSKI, M., SZURKOWSKI, J., & RIKLIS, E. (1990). POLARIZED SPECTRA OF IMMOBILIZED PHYCOBILISOMES ISOLATED FROM VARIOUS CYANOBACTERIA. PHOTOBIOLOGY, 511-517.
• FRACKOWIAK, D., NIEDBALSKA, M., ROMANOWSKI, M., & GRUDA, . (1990). ELECTROCHROMIC EFFECT OF STILBAZOLIUM MEROCYANINES. STUDIA BIOPHYSICA, 123(2), 135-143.
• FRACKOWIAK, D., HENDRICH, W., ROMANOWSKI, M., SZCZEPANIAK, A., & LEBLANC, R. (1988). POLARIZED SPECTRA OF PHOTOSYSTEM-2 PARTICLES IN ISOTROPIC AND STRETCHED POLYVINYLALCOHOL FILMS. PHOTOSYNTHETICA, 21(2), 147-155.
• FRACKOWIAK, D., NIEDBALSKA, M., CEGIELSKI, R., ROMANOWSKI, M., & EROKHINA, L. (1988). POLARIZED SPECTRA OF IMMOBILIZED PHYCOBILISOMES ISOLATED FROM TOLYPOTHRIX-TENUIS. PHOTOSYNTHETICA, 24(2), 201-208.
• SKIBINSKI, A., MARCOTTE, L., EROKHINA, L., ROMANOWSKI, M., & FRACKOWIAK, D. (1988). SPECTRAL PROPERTIES OF PARTIALLY DISSOCIATED AND IMMOBILIZED PHYCOBILISOMES OBTAINED FROM VARIOUS CYANOBACTERIA. PHOTOSYNTHETICA, 24(2), 243-248.
• FRACKOWIAK, D., ROMANOWSKI, M., HOTCHANDANI, S., LEBLANC, L., LEBLANC, R., & GRUDA, . (1987). A PHOTOELECTROCHEMICAL CELL WITH ORIENTED PIGMENT POLYMER COMPLEXES. BIOELECTROCHEMISTRY AND BIOENERGETICS, 19(3), 371-387.
• LORRAIN, L., FRACKOWIAK, D., ROMANOWSKI, M., & LEBLANC, R. (1987). EFFECT OF STRETCHING OF CHLOROPLASTS AND THYLAKOIDS EMBEDDED IN POLYMER-FILMS. PHOTOSYNTHETICA, 21(1), 43-+.
• ROMANOWSKI, M., EROKHINA, L., FRACKOWIAK, D., & LEBLANC, R. (1987). POLARIZED SPECTRA OF ALLOPHYCOCYANIN AND PHYCOCYANIN-ALLOPHYCOCYANIN MIXTURE IN POLYMER MATRIX. PHOTOSYNTHETICA, 21(1), 71-75.

Proceedings Publications

• Howlett, I., Gordon, M., Orsinger, G., Brownlee, J., Romanowski, M., Barton, J., & Kostuk, R. (2015, unknown). Design and implementation of a volume holographic imaging endoscope. In Conference on Lasers and Electro-Optics Europe - Technical Digest, 2015, 7182930.
• Kostuk, R., Howlett, I., Gordon, M., Brownlee, J., De Leon, E., Orsinger, G., Watson, J., Romanowski, M., Hatch, K., Luo, Y., Barbastathis, G., & Barton, J. (2015, unknown). Degenerate volume holographic imaging techniques and instruments for subsurface tissue visualization. In Conference on Lasers and Electro-Optics Europe - Technical Digest, 2015, 7182914.
• Gainer, C., & Romanowski, M. (2010, FEB 2). Diffusion enhanced FRET assay using lanthanide nanoparticles. In BIOPHYSICAL JOURNAL.
• Gainer, C., deSilva, C., & Romanowski, M. (2010, unknown). Augmented microscopy – simultaneous acquisition of bright field and luminescence lifetime images.. In Annual Meeting of the American Society for Laser Surgery and Medicine.
• Kachur, X., Leung, S., Behunin, S., Bobnick, M., & Romanowski, M. (2010, unknown). TARGETED DELIVERY OF GOLD-COATED PLASMON RESONANT LIPOSOMES TO CANCER CELLS. In Annual Meeting of the American Society for Laser Surgery and Medicine.
• Leung, S., & Romanowski, M. (2010, FEB 2). Spectrally Selective Light Induced Release from Gold Coated Liposomes. In BIOPHYSICAL JOURNAL.
• Romanowski, M., Leung, S. J., & Troutman, T. S. (2009, Feb). Plasmon resonant gold-coated liposomes for spectrally coded content release. In Progress in Biomedical Optics and Imaging - Proceedings SPIE, 7190.
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  We have recently introduced liposome-supported plasmon resonant gold nanoshells (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). These plasmon resonant gold-coated liposomes are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery. The present research demonstrates that laser illumination at the wavelength matching the plasmon resonance band of a gold-coated liposome leads to the rapid release of encapsulated substances, which can include therapeutic and diagnostic agents. Leakage of encapsulated contents is monitored through the release of self-quenched fluorescein, which provides an increase in fluorescence emission upon release. Moreover, the resonant peak of these gold-coated liposomes is spectrally tunable in the near infrared range by varying the concentration of gold deposited on the surface of liposomes. Varying the plasmon resonant wavelengths of gold-coated liposomes can provide a method for spectrally-coding their light-mediated content release, so that the release event is initiated by the specific wavelength of light used to illuminate the liposomes. The development of spectrally-coded release can find applications in controlled delivery of multiple agents to support complex diagnostic tests and therapeutic interventions.
• Troutman, T., & Romanowski, M. (2008, January). Biodegradable nanoshells for optical contrast and controlled release. In Biomedical Optics, BIOMED 2008, BSuA3.
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  Abstract: Liposome-supported arrays of gold nanodots exhibit plasmon resonance, making them useful as contrast agents in optical imaging techniques and degradable to components of clearable size. Encapsulated volume can be released with high energy incident light.
• Winkler, A. M., F., P., Troutman, T. S., Backer, M. V., Backer, J. M., Drezek, R. A., Romanowski, M., & Barton, J. K. (2008, January). Fluorescent and scattering contrast agents in a mouse model of colorectal cancer. In Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 6851.
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  Abstract: In previous work we have demonstrated the utility of laser-induced fluorescence (LIF) and optical coherence tomography (OCT) to identify adenoma in mouse models of colorectal cancer with high sensitivity and specificity. However, improved sensitivity to early disease, as well as the ability to distinguish confounders (e.g. fecal contamination, natural variations in mucosal thickness), is desired. In this study, we investigated the signal enhancement of fluorescent and scattering contrast agents in the colons of AOM-treated mice. The fluorescent tracer scVEGF/Cy, targeted to receptors for vascular endothelial growth factor, was visualized on a dual modality OCT/LIF endoscopic system with 1300-nm center wavelength OCT source and 635-nm LIF excitation. Scattering agents were tested with an 890-nm center wavelength endoscopic OCT system. Agents included nanoshells, 120-nm in diameter, and nanorods, 20-nm in diameter by 80-nm in length. Following imaging, colons were excised. Tissue treated with fluorophore was imaged on an epifluorescence microscope. Histological sections were obtained and stained with H&E and silver enhancer to verify disease and identify regions of gold uptake, respectively. Non-specific signal enhancement was observed with the scattering contrast agents. Specificity for adenoma was seen with the scVEGF/Cy dye..

Presentations

• Camp, L., Camp, L., Watson, J., Watson, J., Martirosyan, N., Martirosyan, N., Lemole, G. M., Lemole, G. M., Romanowski, M., & Romanowski, M. (2017, October). Development Of Augmented Microscope For Image Guided Surgery (talk). BMES 2017 Annual Meeting. Phoenix, Arizona: BMES.
• Romanowski, M., & Watson, J. (2017, October). Photothermal Ablation With Plasmon Resonant Liposomes (talk). BMES 2017 Annual Meeting. Phoenix, Arizona: BMES.
• Dawson, P., & Romanowski, M. (2016, June). Characterizing axial resolution while imaging NaYF4:Yb,Tm nanoparticles (talk). 44th ACS Mid Atlantic Regional Meeting. Riverdale, NY: ACS.
• Martirosyan, N., Watson, J., Skoch, J., Lemole, G. M., Romanowski, M., & Anton, R. (2014, unknown). Augmented integration of ICG videoangiography with operative microscope allows simultaneous real-time assessment of vascular structures and blood flow.. 82nd Annual Scientific Meeting of the American Association of Neurological Surgeons. San Francisco: American Association of Neurological Surgeons.
• Martirosyan, N., Watson, J., Skoch, J., Lemole, G. M., Romanowski, M., & Anton, R. (2014, unknown). Integration of ICG videoangiography with operative microscope.. Arizona Neurosurgical Society Annual Meeting. Tucson Arizona: Arizona Neurosurgical Society.
• Orsinger, G., Williams, J., & Romanowski, M. (2014, unknown). Single cell dose-response studied by quantitative optical injection.. NSTI Nanotechnology Conference and Expo. Washington DC.
• Romanowski, M., Orsinger, G., & Williams, J. (2013, unknown). Three Dimensional Model of the Ovarian Cancer Microenvironment.. Biomedical Engineering Society Annual Meeting. Seattle, Washington: Biomedical Engineering Society.

Poster Presentations

• Martirosyan, N., Quon, N., Chambers, R., Romanowski, M., & Lemole, G. M. (2019, October). Experimental Design of Reflex Pupillometer for Continuous, Real-Time Intraoperative & ICU Monitoring. Congress of Neurological Surgeons Annual Meeting. San Francisco, CA: Congress of Neurological Surgeons.
• Chambers, R., Burton, H., Lemole, G. M., & Romanowski, M. (2017, October). Pupillary Device Design for Ocular Cranial Nerve Monitoring. BMES 2017 Annual Meeting.
• Dawson, P., & Romanowski, M. (2018, April). Switch-Like Control of Ultraviolet Emission in Upconversion Nanoparticles. 2018 Materials Research Society Spring Meeting. Phoenix, Arizona: MRS.
• Tecle, D., Knights-Mitchell, S., & Romanowski, M. (2017, October). Folate Receptor-Mediated Targeting of Plasmon Resonant Liposomes. BMES 2017 Annual Meeting. Phoenix, Arizona: BMES.
• Garland, S., Watson, J. R., Martirosyan, N., Lemole, G. M., Romanowski, M., Garland, S., Watson, J. R., Martirosyan, N., Lemole, G. M., & Romanowski, M. (2016, October). Modular Augmented Microscopy with Spatial Light Modulation. Biomedical Imaging and Optics Abstract Sub Track: Imaging Techniques in Neuroscience. Biomedical Engineering Society (BMES) Annual Meeting.

Reviews

• TAO, N., DEFORCE, L., ROMANOWSKI, M., MEZAKEUTHEN, S., SONG, P., & FURUYA, M. (1994. STENTER AND BLEPHARISMA PHOTORECEPTORS - STRUCTURE AND FUNCTION(pp 199-211).

Others

• Kachur, X., Leung, S., & Romanowski, M. (2012, MAR 27). Plasmon resonant liposomes for targeted delivery to cancer cells. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY.