Home > News > Advanced functional materials: a new type of intelligent nano delivery technology with programmed response to tumor molecular signals for precise intracellular delivery of chemotherapy drugs

Advanced functional materials: a new type of intelligent nano delivery technology with programmed response to tumor molecular signals for precise intracellular delivery of chemotherapy drugs

wallpapers News 2020-07-23
At present chemotherapy is still one of the important means of clinical treatment of tumor. However traditional chemotherapeutic small molecule drugs often have low bioavailability serious side effects due to their faster blood clearance rate non-specific tissue distribution in normal tissues. Chemotherapy drug delivery mediated by nanocarriers is a hot topic in the field of cancer treatment which has attracted the attention of scholars at home abroad. The ideal anti-tumor nano drugs should be able to deliver the active drugs to the target of tumor cells accurately so as to play an effective anti-tumor activity. However many physiological pathological barriers in the process of drug delivery seriously affect the efficiency of drug delivery which greatly limits the effectiveness of drug therapy. High interstitial pressure low vascular permeability dense matrix stromal cells in tumor microenvironment are barriers for nanodrugs to enter the deep part of tumor which seriously reduces the effective penetration distribution of nanodrugs to the deep part of tumor. In addition nanodrugs are usually concentrated in lysosomes through endocytosis lysosome pathway after entering tumor cells. How to promote the deep-seated delivery of nano drugs to achieve the efficient intracellular release of active drugs play its therapeutic efficacy is also an important scientific problem to be solved for the accurate intracellular delivery of anti-tumor nano drugs.

State Key Laboratory of natural Biomimetic Drugs Peking University Wang Yiguang research team designed constructed a simple pH / cathepsin B programmed response smart nano drug conjugates (hrns) to overcome many difficulties in drug delivery by programmed response to extracellular intracellular molecular signals of solid tumor To achieve the precise intracellular delivery of chemotherapy drug docetaxel (DTX). Hrns have stable nanostructures (40 nm) in the blood circulation which can be effectively accumulated to the tumor site. The acidic microenvironment of the tumor will trigger the rapid dissolution of hrns nanostructures the rapid reduction of particle size (5 nm) the exposure of positive charges thus promoting the penetration uptake of drugs into the deep part of the tumor. When the polymer drug conjugate is absorbed by tumor cells finally enters lysosomes cathepsin B which is abundant in lysosomes will efficiently cleave the Gly Phe Leu Gly tetrapeptide bond between DTX polymer thus releasing active DTX molecules into the cytoplasm to exert anti-tumor effect. In addition to directly inhibiting the proliferation of tumor cells hrns can also induce the immunogenic death of tumor cells thereby activating DC cells downstream killer T cells triggering anti-tumor immunity in vivo relieving the immunosuppression. Combined with α - PD-1 immunotherapy hrns showed a significant synergistic anti-tumor effect in b16ova mouse tumor model: it can significantly inhibit tumor growth effectively prevent tumor recurrence. It is believed that spkds can provide a simple reliable platform for clinical research of small tumor chemotherapy. The paper was published online in advanced functional materials

the related work was supported by the key R & D program of the Ministry of science technology National Natural Science Foundation of China China Postdoctoral Science Foundation other projects.


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