title: Tumor extracellular acidity activated "off-on" release of bortezomib from a biocompatible dendrimer.
abstract: A nanoparticle with a specific response to tumor extracellular acidity provides a new option in the design of tumor-targeted delivery systems. In this study, we report such a pH-responsive polymer which realizes an "off-on" release of bortezomib in tumor acidic microenvironments. A dendrimer surface is grafted with a neutral shell to reduce its cellular uptake, and its interior is functionalized with catechol moieties. An anticancer drug, bortezomib, is loaded within the dendrimer interior via a boronate-catechol interaction. The bortezomib-loaded dendrimer is non-toxic to a number of cells under physiological conditions, but kills most of the cells in slightly acidic microenvironments. In vivo studies further prove that the bortezomib-loaded dendrimer significantly inhibits tumor growth while causing minimal systemic toxicity to the animals. Since there are a number of potent anticancer drugs containing the boronate structure, the polymeric vector in this study provides a versatile scaffold to design pH-responsive drug carriers for chemotherapy.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, P. R. China. yycheng@mail.ustc.edu.cn.
authors.forename: Mingming
authors.initials: M
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
authors.forename: Naimin
authors.initials: N
authors.lastname: Shao
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry* / Q000494:pharmacology; D000069286:Bortezomib / Q000737:chemistry*; D002396:Catechols / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D002396:Catechols; D050091:Dendrimers; D004337:Drug Carriers; D011108:Polymers; D000069286:Bortezomib; C034221:catechol