title: Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors.
abstract: To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration.
authors.affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China ; 2. College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Dong
authors.affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China ; 3. University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.affiliation: 4. Capital Institute of Pediatrics, Beijing, 100020, China.
authors.forename: Tianyou
authors.initials: T
authors.lastname: Wang
authors.affiliation: 5. Department of Pediatrics, The General Hospital of People's Liberation Army, Beijing, 100853, China.
authors.forename: Suoqin
authors.initials: S
authors.lastname: Tang
authors.affiliation: 2. College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D062346:Molecular Medicine / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D010455:Peptides / Q000378:metabolism*; D013267:Stilbenes / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010455:Peptides; D013267:Stilbenes; D004317:Doxorubicin; C058728:fosbretabulin
keywords: combination cancer therapy; drug resistance.; dual-pH response; polypeptide nanocarriers; site-specific releasing