Redox/pH dual-stimuli responsive camptothecin prodrug nanogels for "on-demand" drug delivery.
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.
['Qu|Ying|Y|', 'Chu|Bingyang|B|', 'Wei|Xiawei|X|', 'Lei|Minyi|M|', 'Hu|Danrong|D|', 'Zha|Ruoyu|R|', 'Zhong|Lin|L|', 'Wang|Mengyao|M|', 'Wang|Fangfang|F|', 'Qian|Zhiyong|Z|']
D000818:Animals D000970:Antineoplastic Agents D002166:Camptothecin D006528:Carcinoma, Hepatocellular D002460:Cell Line D016503:Drug Delivery Systems D065546:Drug Liberation D005782:Gels D006863:Hydrogen-Ion Concentration D008113:Liver Neoplasms D008297:Male D008689:Methacrylates D008807:Mice, Inbred BALB C D008819:Mice, Nude D053758:Nanoparticles D010084:Oxidation-Reduction D011108:Polymers D011355:Prodrugs
Camptothecin Prodrug nanogels Redox-responsive pH-responsive Cancer therapy