title: Self-regulated multifunctional collaboration of targeted nanocarriers for enhanced tumor therapy.
abstract: Exploring ideal nanocarriers for drug delivery systems has encountered unavoidable hurdles, especially the conflict between enhanced cellular uptake and prolonged blood circulation, which have determined the final efficacy of cancer therapy. Here, based on controlled self-assembly, surface structure variation in response to external environment was constructed toward overcoming the conflict. A novel micelle with mixed shell of hydrophilic poly(ethylene glycol) PEG and pH responsive hydrophobic poly(β-amino ester) (PAE) was designed through the self-assembly of diblock amphiphilic copolymers. To avoid the accelerated clearance from blood circulation caused by the surface exposed targeting group c(RGDfK), here c(RGDfK) was conjugated to the hydrophobic PAE and hidden in the shell of PEG at pH 7.4. At tumor pH, charge conversion occurred, and c(RGDfK) stretched out of the shell, leading to facilitated cellular internalization according to the HepG2 cell uptake experiments. Meanwhile, the heterogeneous surface structure endowed the micelle with prolonged blood circulation. With the self-regulated multifunctional collaborated properties of enhanced cellular uptake and prolonged blood circulation, successful inhibition of tumor growth was achieved from the demonstration in a tumor-bearing mice model. This novel nanocarrier could be a promising candidate in future clinical experiments.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Institute of Polymer Chemistry, Nankai University , Tianjin 300071, People's Republic of China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Gao
authors.forename: Tangjian
authors.initials: T
authors.lastname: Cheng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Jinjian
authors.initials: J
authors.lastname: Liu
authors.forename: Cuihong
authors.initials: C
authors.lastname: Yang
authors.forename: Liping
authors.initials: L
authors.lastname: Chu
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rujiang
authors.initials: R
authors.lastname: Ma
authors.forename: Linqi
authors.initials: L
authors.lastname: Shi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; C507253:poly(beta-amino ester); D011092:Polyethylene Glycols