Anti-tumor Activities Of Nanoparticle Loaded With Photosensitizer

Nanosized drug delivery systems(Nano-DDSs) have attracted extensive attentions due to its targeting ability, protection for drug, controlled or sustained release, less toxic side effects, etc. They are particularly useful in cancer therapy as the nano-sized particles could accumulate in tumor sites through enhanced permeability and retention effect(EPR), delivering more anti-cancer drugs into the tumor. Importantly, Nano-DDSs can integrate different modes of therapy to realize more effective therapeutic efficiency. Thus, more and more researchers pay attention to the combination of different therapeutic strategies with Nano-DDSs and antineoplastic agents.Photodynamic therapy(PDT) is an attractive method in clinic due to its less injury, better selectivity, etc. The two major problems that hinder the application of PDT are the poor targeting ability and shallow penetration of light. Boron dipyrromethene(Bodipy) is one of second generation photosensitizers which has high singlet oxygen quantum yield, better photo-stability, maximum absorbance in Near-infrared region(NIR), less toxic and side effects, etc. Here we report a nanosized drug delivery system using Bodipy as a model compound, exhibiting an enhanced photodynamic therapy in tumor site. In addition, the Bodipy nanocomposites also achieve the photothermal effect through the adjustment of Bodipy aggregation. Interestingly, the Bodipy nanocomposites exhibit effective synergistic photodynamic/photothermal therapy of tumors. The contents of my thesis are as follows:Chapter1: Recent progress in tumor therapy, basic information and advances of PDT/PTT and the nanosized drug delivery systems for PDT/PTT.Chapter2: Physicochemical properties of micelles and vesicles loaded with Bodipy as a model compound, and block polymers of PEG45-b-PCL66, PEG45-PCL60-PNIPAM33 were used to prepare vesicles and micelles as carriers through various methods. Dynamic light scattering(DLS) revealed the size of micelles and vesicles at less than 100 nm, and the Bodipy-loaded micelles and vesicles exhibit qualified size-stability, photo-stability and chemical-stability. The aggregation of Bodipy in micelles and vesicles results in a red-shift of maximum absorbance, which can change the photo-physical properties. In addition, the micelles and vesicles display effective singlet oxygen generation ability and photothermal effect.Chapter3: The cellular uptake exhibited micelles and vesicles’ superiority in taking in Bodipy through clathrin-mediated pathway. Cytotoxicity exhibited two different ways that induced cell death and AO/EB staining verified the mechanism of cell death. Sub-cellular distribution verified a high co-localization within lysosomes of micelles and vesicles, AO staining furtherly demonstrated the lysosome disruption of micelles and vesicles., DHE staining elucidated the existence of singlet oxygen of cells incubated with Bodipy, micelles and vesicles when suffer irradiation.Chapter4: Pharmacokinetics exhibited the long circulation action of micelles and vesicles in vivo, Biodistribution elucidated better tumor-targeting ability of micelles and vesicles, tissue ROS test and thermal imaging exhibited PDT and PTT both play part in tumor therapy, tumor inhibition elucidated the applicability and advantage of micelles and vesicles, H&E staining of Bodipy, micelles and vesicles proved the irreversible histological damage that micelles and vesicles induced in tumor site under irradiation.