title: PH responsive polypeptide based polymeric micelles for anticancer drug delivery.
abstract: A pH-responsive polymeric micelle based on poly(aspartamide) derivative was explored as an efficient acid-triggered anticancer drug delivery system. Poly(α,β-l-asparthydrazide) (PAHy) was prepared by aminolysis reaction of polysuccinimide with hydrazine hydrate. Poly(ethylene glycol) and aliphatic chain (C18) were conjugated onto PAHy to afford an amphiphilic copolymer with acid-liable hydrazone bonds. The structure of the resulting copolymer and its self-assembled micelles were confirmed by (1) H NMR, FTIR, DLS, and TEM. Furthermore, doxorubicin (DOX) was loaded into the polymeric micelles via the hydrophobic interaction between the C18 group and DOX molecules, and the π-π staking between the hydrazone conjugated DOX and free DOX molecules. Results showed that the DOX loaded nanoparticle (NP) was relatively stable under physiological conditions, while the DOX was quickly released in response to acidity due to the shedding of mPEG shells and dissociating of C18 segments because of the pH-cleavage of intermediate hydrazone bonds. In addition, the DOX loaded micelles presented a high cytotoxic activity against tumor cells in vitro. This pH responsive NP has appeared highly promising for the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy.
authors.affiliation: Key Laboratory of Functional Polymer Materials of MOE, Institute of Polymers, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China.
authors.forename: Dongping
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Functional Polymer Materials of MOE, Institute of Polymers, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China.
authors.forename: Bingqiang
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Functional Polymer Materials of MOE, Institute of Polymers, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Han
authors.affiliation: Key Laboratory of Functional Polymer Materials of MOE, Institute of Polymers, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Functional Polymer Materials of MOE, Institute of Polymers, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China.
authors.forename: Xinchen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Polymer Materials of MOE, Institute of Polymers, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D016503:Drug Delivery Systems; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D009757:Nylons / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D006834:Hydrazines; D008823:Micelles; D009757:Nylons; D011108:Polymers; C114303:alpha,beta-polyasparthydrazide; D004317:Doxorubicin
keywords: drug delivery; hydrazone; micelle; pH-sensitive; poly(aspartamide)