title: cRGD-Modified Benzimidazole-based pH-Responsive Nanoparticles for Enhanced Tumor Targeted Doxorubicin Delivery.
abstract: Finding a smart cancer drug delivery carrier with long blood circulation, enhanced cancer targeting, and quick drug release in tumors is critical for efficient cancer chemotherapy. Herein, we design a cRGD-polycarboxybetaine methacrylate-b-polybenzimidazole methacrylate (cRGD-PCB-b-PBBMZ) copolymer to self-assemble into smart drug-loaded nanoparticles (cRGD-PCM NPs) which can target αvβ3 integrin overexpressed cancer tissue by cRGD peptide unit and release drug quickly in cancer cells by protonation of benzimidazole groups. The outer PCB layer can resist protein adhesion, and there are only about 10% of proteins in mouse serum adhered to the surface of PCM NPs. With the pKa value of 5.08 of the benzimidazole units, DOX can be released from NPs in pH 5.0 PBS. cRGD-PCM NPs can bring more DOX into HepG2 cells than nontargeting PCM NPs, and there has high DOX release rate in HepG2 cells because of the protonation of benzimidazole groups in endosome and lysosome. MTT assay verifies that higher cellular uptake of DOX causes higher cytotoxicity. Furthermore, the results of ex vivo imaging studies confirm that cRGD-PCM/DOX NPs can successfully deliver DOX into tumor tissue from the injection site. Therefore, the multifunctional cRGD-PCM NPs show great potential as novel nanocarriers for targeting cancer chemotherapy.
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College , Tianjin 300192, People's Republic of China.
authors.forename: Jinjian
authors.initials: J
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College , Tianjin 300192, People's Republic of China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College , Tianjin 300192, People's Republic of China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College , Tianjin 300192, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College , Tianjin 300192, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chu
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College , Tianjin 300192, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors.forename: Liandong
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, People's Republic of China.
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College , Tianjin 300192, People's Republic of China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001562:Benzimidazoles; D004317:Doxorubicin; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms
chemical_list: D001562:Benzimidazoles; D004337:Drug Carriers; D004317:Doxorubicin
keywords: benzimidazole; cancer targeting; doxorubicin; nanocarriers; pH-responsive