Redox/pH dual-stimuli responsive camptothecin prodrug nanogels for "on-demand" drug delivery. 2019

Ying Qu, and Bingyang Chu, and Xiawei Wei, and Minyi Lei, and Danrong Hu, and Ruoyu Zha, and Lin Zhong, and Mengyao Wang, and Fangfang Wang, and Zhiyong Qian
Department of Hematology and Research Laboratory of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.

At present, chemotherapy remains to be one of the most important therapeutic approaches for malignant tumors. The tumor microenvironment(TME)-responsive intelligent drug delivery systems are still the hot research topics in delivering chemotherapeutic drugs. Camptothecin (CPT) possesses very strong antitumor activities, but its clinical application is hindered by its poor water-solubility and serious toxic side effects. Herein, a new intelligent and TME-responsive P(CPT-MAA) prodrug nanogel was developed for delivering CPT and reducing its side effects. P(CPT-MAA) prodrug nanogels were prepared with methacrylic acid (MAA), CPT monomer (CPTM) and N,N'-methylenebisacrylamide (Bis) via distillation-precipitation polymerization, in which CPT was covalently conjugated into the nanogels via redox-responsive disulfide linker. The as-prepared nanogels were spherical shapes with uniform size and narrow size distribution. With the help of redox-responsive property of disulfide linker and pH-responsive property of PMAA, the release of CPT from prodrug nanogels was redox/pH-dual dependent and could be accelerated by the increased concentration of GSH and the decreased pH value, which were favorable to realize the "on-demand" drug release in tumor cell and tumor tissue microenvironment. Furthermore, P(CPT-MAA) prodrug nanogels exhibited superior antitumor activity both in vitro and in vivo without observed side effects. Hence, the prepared P(CPT-MAA) prodrug nanogels may be a promise delivery system for chemotherapeutic agents.

UI MeSH Term Description Entries
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008297 Male Males
D008689 Methacrylates Acrylic acids or acrylates which are substituted in the C-2 position with a methyl group. Methacrylate
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D011108 Polymers Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS). Polymer
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D002166 Camptothecin An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. Camptothecine
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell

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