title: Polymer Nanoparticles Modified with Photo- and pH-Dual-Responsive Polypeptides for Enhanced and Targeted Cancer Therapy.
abstract: The cationic nature of cell penetrating peptides (CPPs) and their absence of cell selectivity restrains their applications in vivo. In this work, polymer nanoparticles (NPs) modified with photo- and pH-responsive polypeptides (PPPs) were successfully developed and respond to near-infrared (NIR) light illumination at the tumor site and a lowered tumor extracellular pH (pHe). In PPPs, the internalization function of CPPs (positively charged) is quenched by a pH-sensitive inhibitory peptide (negatively charged), which is linked via a photocleavable group. Small interfering RNA (siRNA) was loaded into NPs by a double-emulsion technique. In vivo experiments included siRNA loading, cellular uptake, cell apoptosis, siRNA transfection, tumor targeting delivery, and the in vivo antitumor efficacy. Results showed that the prepared PPP-NPs could selectively accumulate at the tumor sites and internalized into the tumor cells by the NIR light illumination and the lowered pHe at the tumor site. These studies demonstrated that PPP-NPs are a promising carrier for future tumor gene delivery.
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.|Department of Pharmacy, Wuhan General Hospital of Guangzhou Command , Wuhan 430070, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.|Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D011108:Polymers; D034741:RNA, Small Interfering
keywords: cell-penetrating peptides; photo- and pH-responsive polypeptides; small interfering RNA; tumor targeting nanoparticles