Research On Intelligent Nano Drug Carriers

Chemotherapy is a treatment method of killing cancer cells by chemical drugs to control the proliferation,infiltration and metastasis of cancer cells.Paclitaxel and paclitaxel derivatives are chemotherapy drugs that are widely used in the treatment of many cancers.However,many anticancer drugs are high hydrophobic ity result in poor solubility and bioavailability.So we need to use all kinds of preparation technology for processing.At present,many of the anti-cancer drug preparations are not highly selective,not only kill cancer cells but also damage the body's normal cells and organ function,bringing pain to patients.The application of nanotechno logy in cancer treatment has made great progress in recent years.Through integrating the combination chemotherapy of docetaxel with pH-sensitive materials in this project,novel smart pH-sensitive nanoparticles of PLA-mPEG2000/TPGS3350-PHis-Folate for enhanced effect of chemotherapy are developed.Polyethylene glycol(PEG)is decorated on the surface of nanocarriers in order to prolong the circulation of nanoparticles in blood;the pH-sensitive material of poly(L-histidine)is utilized in nanoparticles for the intelligent purposes:under normal physiological pH,the targeting molecule of folate can be hidden into the layer of PEG in nanoparticles,which closes the active targeting function of nanoparticles;but in weak acid of tumor tissue,poly(L-histidine)is protonated to expose folate on the surface of nanoparticles,opening the active targeting function;next,nanoparticles are internalized by cells via folate receptor-mediated endocytosis;finally,poly(L-histidine)in endosome/lysosome begins to dissociate,leading to quick intracellular drug release.The features of the PLA-mPEG2000/TPGS3350-PHis-Folate nanoparticles such as morphology,particle size,Zeta,drug loading content,in vitro release,in vitro cytotoxicity and in vitro cellular uptake are further investigated.The pH sensitivity and targeting effect was investigated in vitro by 4T1 murine breast cancer cells uptake of coumarin-6-loaded nanoparticles at different pH observing through CLSM.The CCK-8 assay showed docetaxel-loaded pH-sensitive nanoparticles had higher cytotoxicity at pH 5.8 than that at pH 7.4.Nanoparticles designed in this work have multple functions such as active targeting,long circulation and easy internalization by cells simultaneously,and rapid intracellular drug release,which significantly improve the anticancer effects of combination chemotherapy of docetaxel and reduce toxic side effects.There is a huge potential for pH-sensitive nanopartic les of PLA?mPEG2000/TPGS3350-PHis-folate to apply for the efficient treatment of cancer.In the aiticle,we also prepared PLA-PEGiooo/TPGS-FOL nanoparticles loaded with polyoxometalates,which improved the water solubility and stability of polyoxometallates.In this way we improved the anticancer effects of polyoxometallates remarkably,and reduced its toxic and side effects on normal tissues and organs.