Self-Assembled Nano-Photosensitizers Based On Amino Acid Derivatives

Photosensitizers play a key role in photodynamic therapy.At present,the photosensitizers used clinically are mainly small organic molecules,which have problem of less accumulation in target tumors.With the development of nanotechnology,the use of nanocarriers for drug delivery and solving the accumulation of organic small molecule photosensitizers in target tumors has become a research hotspot.Currently,the self-assembly strategy is considered to be a very attractive solution because it can achieve higher drug loads.Among various self-assembled monomers,amino acids with diverse properties have attracted more and more attention.Amino acids and peptides composed of amino acids can form self-assembled nanostructures that are easy to adjust.Due to their good biocompatibility,low immunogenicity,and easy availability,they are widely used in drug delivery.The delivery research of molecular photosensitizers has just started.In this thesis,two kinds of nano photosensitizers were developed for tumor photodynamic therapy based on the co-assembly of amino acid derivatives and photosensitizers.We used the amphiphilic amino acid 9-fluorenylmethoxycarbonyl-L-lysine（Fmoc-L-Lys）to co-assemble with the small molecule photosensitizer o-FL to prepare the responsive nano-photosensitizer.FKNPs.The assembly process is driven by non-covalent interactions between amphiphilic amino acids and photosensitizers.Since the photosensitizer o-FL itself has become one of the components of the photosensitizer delivery system,the loading capacity of the photosensitizer has been increased.The assembled nano-photosensitizer improves the poor water solubility of the photosensitizer.Affected by the tumor microenvironment,the non-covalent interaction between molecules changes,leading to the disassembly of FKNPs to release the photosensitizer for subsequent photodynamic therapy.The strategy of driving the co-assembly and disassembly of amphiphilic amino acids and photosensitizers through weak intermolecular interactions has been fully applied in the design of nano photosensitizers.The highly hydrophobic Fmoc-L₃-OMe and the fluorescein derivative FL,a small molecule photosensitizer,self-assemble to form a nano photosensitizer through non-covalent interactions such as hydrophobic interactions andπ-πstacking.The obtained nano-photosensitizer FLNPs disperse FL between Fmoc-L₃-OMe,avoiding the self-quenching induced by the self-aggregation of hydrophobic FL,thereby generating singlet oxygen to destroy cell homeostasis and induce cancer cell apoptosis.The non-quenching photosensitizer delivery method can effectively avoid the incomplete release of the responsive nano photosensitizer,thereby improving the efficiency of photodynamic therapy.In summary,the thesis uses the strategy of self-assembly of amino acid derivatives to try a responsive and non-quenching nano-delivery method of small molecule photosensitizers,and has made preliminary progress,laying the foundation for subsequent work.