Exploring nanosystems for biomedical applications focusing on photodynamic therapy and drug delivery

作者: Vladimir Kirejev

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摘要: The increasing incidences of cancer and related deaths call for the development new improved treatment modalities. Photodynamic therapy (PDT) today is an alternative to conventional treatments, but has limitations. This thesis explores different nanosystems with aim improve PDT focusing on spectroscopic ex vivo studies. Nanosystems capable efficient photodynamic action in anaerobic or hypoxic conditions are gaining much attention. Constructs cyclodextrin polymer encapsulating anthracenenitroaniline conjugates, that can release nitric oxide (NO) radicals upon irradiation, were investigated this thesis. It was demonstrated concomitant increase fluorescence be used dosimetry NO release. Pulsed near-infrared laser light photorelease by two-photon excitation process along high phototoxicity (observed cell mortality >90%) make nanosystem a promising technique (paper I). A multimodal consisting polymer, adamantyl-nitroaniline, zinc phthalocyanine tetrasulfonate evaluated II). Multiphoton microscopy showed cytosolic distribution vitro cells ability penetrate into skin. In addition, combinatorial phototoxic effect elicited singlet oxygen (cell >90%), indicates potential PDT. Herein, it conjugation water non-soluble photosensitizer (mTHPP) enhance its aqueous solubility monomerization, thereby leading photophysical properties environment III).It also shown facilitates skin penetration vivo. Fluorescence lifetime imaging accumulation monomeric conjugate cytoplasm cells. been suggested enhancement achieved combination gold nanoparticles; however, investigations demonstrate lack using protoporphyrin IX PEGylated goldnanorods IV). Cell viability studies combined measurements confirming energy transfer between nanoparticles photosensitizer. Incubation combining aminolevulinic acid nanorods slightly elevated efficiency, however most likely attributed enhanced delivery rather than transfer. Finally, nanoparticle labelled lactose moieties explored tumour-specific (Paper V). visualise multiphoton-induced luminescence from particles loaded epithelial keratinocytes. study demonstrates uptake obtained targeting galecin-3, known overexpressed tumour Taken together, work presents several Of particular interest photoreleasing conditions. Furthermore, biodistribution targeted clever design systems, presenting interesting approaches aid restraining acute problem worldwide occurrence cancer.

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