Preparation And Application Of Porphyrin Derivative Nanoparticles For Enhanced Photodynamic Therapy

Cancer is still the leading cause of human death.There are still many shortcomings in traditional cancer treatment methods,such as large toxic,side effects,and serious damage to human functions.Photodynamic therapy?PDT?as a new type of cancer treatment has become an excellent cancer treatment for its non-invasive advantages.Photosensitizers are an important part of photodynamic therapy.Currently,porphyrin and its derivatives are currently the most widely used photosensitizers.However,the poor water solubility limited the applications of porphyrin photosensitizers in biomedicine.Therefore,the construction of nanocarriers for carrying porphyrin photosensitizers to improve their photodynamic effects and expand their biomedical applications has become a new research hotspot.In this dissertation,polyglutamic acid,which can respond to the release of sulfur dioxide gas by glutathione,was employed as a carrier.By constructing porphyrin derivative nanogels with excellent properties,the photodynamic effects of porphyrin photosensitizers can be enhanced,and their applications in the field of biomedicine can be expanded.The main research contents of this paper are as follows:?1?In tumor cells,overexpressed glutathione?GSH?will inhibit cancer treatments based on reactive oxygen species?ROS?,such as PDT.In this chapter,we explore a promising strategy to enhance the PDT effect by consuming GSH in tumor cells and simultaneously releasing sulfur dioxide gas to regulate the redox environment balance in tumor cells.In detail,a small molecular prodrug,N-?3-azidopropyl?-2,4-dinitrobenzenesulfonamide?AP-DNs?was conjugated onto methoxy poly?ethylene glycol?-block-poly??-propargyl-L-glutamate??mPEG-PPLG?backbone to prepare an amphiphilic polymer prodrug of sulfur dioxide?mPEG-PLG?DNs??.The obtained mPEG-PLG?DNs?could encapsulate photosensitizer 5-?4-aminophenyl?-10,15,20-triphenylporphyrin?Por-NH₂?for photodynamic therapy.The photosensitizer loading efficiency was higher up to 95.4%.The formed nanoparticles with excellent biocompatibility and carrying Por-NH₂ can be effectively internalized by 4T1 cells.In tumor cells,over-expressed glutathione triggers the production of sulfur dioxide gas,which can not only induce apoptosis,but also increase intracellular ROS levels.In addition,the photosensitizer loaded in mPEG-PLG?DNs?will produce reactive oxygen species?ROS?under light irradiation,resulting in tumor cell apoptosis or necrosis.In vitro and in vivo experiments strongly prove that the combination of sulfur dioxide gas therapy and photodynamic therapy can effectively inhibit the growth of tumor cells.This collaborative therapy platform can provide effective methods to regulate the balance of redox environment in tumor cells and achieve satisfactory tumor treatment results..?2?Porphyrin-based nanogels were prepared by utilizing the cross-linking properties of the nanogels,which solved the problems of the hydrophobic properties of porphyrins and their easy aggregation caused quenching?ACQ?.The porphyrin-based nanogels possessed excellent biocompatibility in the dark.Under the light conditions,it would show much higher cytotoxicity than that of the porphyrin before modification.Moreover this nanogels carriers can effectively enhance the photodynamic treatment effect of porphyrins.In this chapter,the porphyrin-based nanogels successfully prevented the ACQ effect of the photosensitizers in hydrophilicity environment and enhanced the photodynamic effects of the photosensitizers.