Synthesis And Application Of Light-Responsible Polythiocarbamate Amphiphilic Block Copolymers

Chemotherapy is one of the most effective treatments for malignant tumors.However,small molecule chemotherapeutic drugs have disadvantages such as poor water solubility and toxic side effects on normal tissues,which reduce the effect of chemotherapeutic drugs on tumor treatment.In response to these problems,Stimulusresponsive nano-drug carriers has been extensively studied.On the one hand,these nano-drug carriers are mainly composed of amphiphilic block copolymers,which can self-assemble to form micelles,vesicles and other assemblies that can encapsulate small-molecule drugs within the assembled extractor cores,thus increasing the blood circulation and tumor enrichment of drugs.On the other hand,due to the stimulus responsiveness of the carrier,the loaded drug can be released under certain specific stimuli to achieve precise delivery and release of chemotherapeutic drugs.In this paper,a light-responsive amphiphilic block polymer was designed and synthesized for the delivery of small molecule antitumor drugs.1.A kind of poly(thiocarbamate)with an o-nitrobenzyl end group(NB-PTUOH)was synthesized by an addition polycondensation reaction,and then an amphiphilic block copolymer NB-PTU-PEG was synthesized by coupling NB-PTUOH with a polyethylene glycol chain segment.The o-nitrobenzyl at the end of the copolymer confers light responsiveness to the copolymer,and the breakage of the onitrobenzyl under UV irradiation causes programmed depolymerization of the subsequent poly(thiocarbamate)chain segments.GPC results show that the polymer can undergo depolymerization after 20 min of UV irradiation(365 nm,2.7 mW/cm2)and complete depolymerization after 8 h.The amphiphilic polymer could selfassemble in water to form spherical micelles with a diameter of 167 nm.DLS and TEM results showed that the micelles could also dissociate under the same conditions of UV irradiation;it was further demonstrated by the NB-PTU-PEG nanomicelles loaded with Nile Red that the loaded Nile Red could be released under UV irradiation.2.A nano-drug delivery system NB-PTU-PEG/MTX was constructed by encapsulating the small molecule antitumor drug methotrexate(MTX)in the core of NB-PTU-PEG nanomicelles.The stability and biocompatibility of the nanomicelles as drug delivery carriers were investigated.The results showed that the nanomicelles could be stable in PBS solution for more than 96 h.The cell killing effect of the nanomicelles and the UV light source used to trigger the degradation was negligible.Then,the in vitro anti-tumor ability and biodistribution of the nano-drug delivery system were investigated.The results showed that the killing ability of the nano-drug delivery system on 4T1 tumor cells after UV light triggering was comparable to that of free MTX,and it could be enriched in the tumor tissues of 4T1 tumor-bearing mice after tail vein injection.