Biotin-Decorated And Stimuli-responsive Prodrug Based Biodegradable Amphililic Polymer For Intracellular Drug Delivery

Aliphatic polyester often used as a biomedical polymer drug carrier material because of its good biocompatibility and biodegradability. Preparation prodrugs to load the drug molecules by physical or chemical bond package drugs can improve the defects of antitumor drug molecules such as low utilization rate, poor solubility and toxicity. On this basis, the design of bonds with environmental sensitivity can improve availability of antitumor drugs and reduce the phenomenon of critical interpretation in the process of drug release. In the drug delivery system, the introduction of a target molecule reduces aggregation of drug molecules at non-target sites therefore anticancer drugs molecule delivered can be directed to the tumor cells, which greatly reduces the cytotoxicity of anticancer drugs to the body's normal cells. Therefore, the design and synthesis of a targeted, biodegradable, bio-safety drug delivery system has become a hot research now.In this article, we choosed biotin as the target molecule and synthesizsed functionalized lactide monemer.Through ring-opening polymerization of functionalized lactide monemer to synthesizse functionalized PLA by using biotin as a initiator. Introducing the short-chain OEG as a hydrophilic segment, which reacted with polylactide by azide-ene cycloaddition reaction. We used the polymer as a initiator and synthesizsed the targeted functionalized PLA copolymers P(LA-g-OEG)-b-PLA through ring-opening polymerization. We prepared block copolymer containing pendant hydroxyl groups by mercapto-ene click reaction followed by ring-opening reaction between acid anhydride and hydroxyl prepared a block copolymer containing pendant carboxyl. Finally, we prepared camptothecin prodrug systemthe through camptothecin bonded to amphiphilic block copolymers by classic DCC condensation reaction. Dynamic light scattering results showed prodrug assembled into micelles of about several tens of nanometers. Drug release experiments in vitro verified redox response of the prodrug. MTT experimental results show that the polymer can be used as a drug carrier because of the low toxicity and the prodrugs have a good killing effect to tumor cells in a certain concentration range and the prodrug with a target molecule has a more obvious.In this article, we also prepared a DOX prodrug with pH-responsive. Drug release experiments in vitro verified pH-responsive of the prodrug. MTT experimental results show that the polymer can be used as a drug carrier because of the low toxicityand the prodrugs have a good killing effect to tumor cells in a certain concentration range and the prodrug with a target molecule has a more obvious. CLSM results show that the prodrugs with the target molecule into the nuclei of tumor cells efficiency is significantly better than non-targeted prodrug. In summary, polymer prodrug synthesized in this paper has good prospects in the field of anti-tumor.