1. Core–shell polymeric nanoparticles co-loaded with photosensitizer and organic dye for photodynamic therapy guided by fluorescence imaging in near and short-wave infrared spectral regions
- Author
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L. O. Vretik, Svitlana M. Levchenko, Junle Qu, J. L. Bricks, Mykhaylo Yu. Losytskyy, Yu. L. Slominskii, Roman Ziniuk, Tymish Y. Ohulchanskyy, Hao Xu, Artem Yakovliev, Oksana Chepurna, and O. A. Nikolaeva
- Subjects
Chlorophyll ,Male ,Fluorescence-lifetime imaging microscopy ,Polymers ,medicine.medical_treatment ,Acrylic Resins ,Pharmaceutical Science ,Medicine (miscellaneous) ,Photodynamic therapy ,02 engineering and technology ,Photochemistry ,01 natural sciences ,Applied Microbiology and Biotechnology ,law.invention ,Mice ,chemistry.chemical_compound ,law ,Neoplasms ,Tissue Distribution ,Photosensitizer ,Mice, Inbred BALB C ,Photosensitizing Agents ,Molecular Structure ,Singlet Oxygen ,Singlet oxygen ,Optical Imaging ,Short wave infrared fluorescence bioimaging ,021001 nanoscience & nanotechnology ,Fluorescence ,lcsh:R855-855.5 ,Molecular Medicine ,0210 nano-technology ,Hydrophobic and Hydrophilic Interactions ,Biodistribution ,Materials science ,lcsh:Medical technology ,Cell Survival ,Drug Compounding ,lcsh:Biotechnology ,Biomedical Engineering ,Mice, Nude ,Antineoplastic Agents ,Bioengineering ,Polymeric nanoparticles ,010309 optics ,Nanocapsules ,Confocal microscopy ,Cell Line, Tumor ,lcsh:TP248.13-248.65 ,0103 physical sciences ,medicine ,Animals ,Humans ,Poly-N-isopropylacrylamide ,Fluorescent Dyes ,Research ,Photobleaching ,Photochemotherapy ,chemistry ,Polystyrenes ,Electronic excitation energy transfer - Abstract
Background Biodistribution of photosensitizer (PS) in photodynamic therapy (PDT) can be assessed by fluorescence imaging that visualizes the accumulation of PS in malignant tissue prior to PDT. At the same time, excitation of the PS during an assessment of its biodistribution results in premature photobleaching and can cause toxicity to healthy tissues. Combination of PS with a separate fluorescent moiety, which can be excited apart from PS activation, provides a possibility for fluorescence imaging (FI) guided delivery of PS to cancer site, followed by PDT. Results In this work, we report nanoformulations (NFs) of core–shell polymeric nanoparticles (NPs) co-loaded with PS [2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a, HPPH] and near infrared fluorescent organic dyes (NIRFDs) that can be excited in the first or second near-infrared windows of tissue optical transparency (NIR-I, ~ 700–950 nm and NIR-II, ~ 1000–1350 nm), where HPPH does not absorb and emit. After addition to nanoparticle suspensions, PS and NIRFDs are entrapped by the nanoparticle shell of co-polymer of N-isopropylacrylamide and acrylamide [poly(NIPAM-co-AA)], while do not bind with the polystyrene (polySt) core alone. Loading of the NIRFD and PS to the NPs shell precludes aggregation of these hydrophobic molecules in water, preventing fluorescence quenching and reduction of singlet oxygen generation. Moreover, shift of the absorption of NIRFD to longer wavelengths was found to strongly reduce an efficiency of the electronic excitation energy transfer between PS and NIRFD, increasing the efficacy of PDT with PS-NIRFD combination. As a result, use of the NFs of PS and NIR-II NIRFD enables fluorescence imaging guided PDT, as it was shown by confocal microscopy and PDT of the cancer cells in vitro. In vivo studies with subcutaneously tumored mice demonstrated a possibility to image biodistribution of tumor targeted NFs both using HPPH fluorescence with conventional imaging camera sensitive in visible and NIR-I ranges (~ 400–750 nm) and imaging camera for short-wave infrared (SWIR) region (~ 1000–1700 nm), which was recently shown to be beneficial for in vivo optical imaging. Conclusions A combination of PS with fluorescence in visible and NIR-I spectral ranges and, NIR-II fluorescent dye allowed us to obtain PS nanoformulation promising for see-and-treat PDT guided with visible-NIR-SWIR fluorescence imaging.
- Published
- 2020