Nanodrug Delivery Systems Based On A Novel Conjugated Polymer For Tumor Photothermal Therapy

Cancer has become a serious threat to life and health all over the world due to its high mortality and invasiveness.The current treatment of cancer mainly includes chemotherapy,radiotherapy,and surgery,all of which have their own drawbacks.As a new non-invasive treatment method,photothermal therapy is increasingly used in tumor treatment.Photothermal therapy increases the temperature by converting light energy into heat energy and inhibits the growth of tumor cells by using the sensitivity of tumor cells to temperature.Compared with other treatments,photothermal therapy can precisely target the lesions with a steerable dose of external laser irradiation,thereby minimizing the damage to the surrounding healthy tissue.In tumor photothermal therapy,the selection of photothermal reagent is very important.The ideal photothermal reagent should have high photothermal conversion ability,good biocompatibility,low biological toxicity,and easy to be uptaken by tumor cells.Most of the conjugated polymer materials not only have good photothermal stability and photothermal conversion ability but also show good biocompatibility and less toxicity.Therefore,they are usually regarded as ideal photothermal reagents.In this study,a novel donor-acceptor conjugated polymer PDPPDTP was designed and synthesized by Donor-Acceptor(D-A)polymerization.This novel polymer has good photothermal conversion ability in the near-infrared region of 700-900 nm.Based on this novel conjugated polymers,the work are summarized as follows:(1)A biodegradable PEG-PCL polymer was successfully synthesized and a novel PEG-PCL@PDPPDTP micelles were obtained by encapsultion the novel conjugated polymer PDPPDTP with PEG-PCL;The in vitro performance of the nanomicelles were characterized,demonstrating that the nanomicelles had good morphology and size distribution,and could efficiently load PDPPDTP;in vitro photothermal performance experiments of the nanomicelles proved that the nanomicelles have efficient photothermal conversion capabilities;Finally,in vitro cell experiments demonstrated that the nanomicelles not only showed good biocompatibility and low toxicity but also can effectively inhibit the proliferation of breast cancer cells under the near-infrared light irradiation at 808 nm.(2)RGD-PEG-PCL polymer was successfully synthesized by conjugation of the cyclic RGD on the hydrophilic end of PEG-PCL;a novel RGD-PEG-PCL@PDPPDTP micelles which can specifically recognize tumor cells MDA-MB-231 was prepared by encapsulation the novel conjugated polymer PDPPDTP with the mixture of PEG-PCL and RGD-PEG-PCL;The in vitro performance of the nanomicelles were characterized,proving that the nanomicelles also had good morphology and size distribution,and could efficiently load PDPPDTP;the in vitro cellular uptake experiments of the nanomicelles have proved that the nanomicelles have active targeting ability to MDAMB-231 tumor cells;Finally,in vitro cell experiments have demonstrated that the targeting ability of the nanomicelles can enhance the photothermal effect on tumor cells.(3)The mPEG-P[CL-co-MPC/TMA]-Pt polymer was successfully synthesized by chelating the cisplatin on the synthesized mPEG-b P[CL-co-MPC/TMA] polymer containing carboxyl;a novel mPEG-b P[CL-co-MPC/TMA]-Pt@PDPPDTP micelles with chemotherapeutic/photothermal therapy ability was prepared;The in vitro performance of the nanomicelles were characterized,proving that the nanomicelles had good morphology and particle size distribution,and could efficiently load both cisplatin and PDPPDTP;in vitro cell experiments have demonstrated that the cisplatin drug treatment and photothermal therapy have a synergistic effect,and the temperature generated by photothermal therapy can promote the release of cisplatin drug.In this research,a nano-drug delivery system was systematically constructed to deliver a novel conjugated polymer PDPPDTP and applied in the tumor therapy.First,the conjugated polymer PDPPDTP was applied in tumor photothermal therapy as a novel nanophotothermal reagent and the growth of tumor cells was successfully inhibited.Then,a new nanophotothermal reagent with active targeting ability was successfully synthesized by modifying the coating polymer,which was applied in the tumor-targeted photothermal therapy.Furthermore,a novel nanomicelles combining cisplatin with the photothermal reagent PDPPDTP was synthesized and applied in the tumor chemotherapy/photothermal therapy,achieving the efficient inhibition of tumor cells under lower doses of photothermal reagents and cisplatin drugs.This study provides a new idea for the research of tumor treatment and development of nano-drug systems.