title: Doxorubicin-loaded polypeptide nanorods based on electrostatic interactions for cancer therapy.
abstract: An amphiphilic anionic polypeptide, methoxypolyethylene glycol-poly (glutamic acid) (mPEG-PGA), was synthesized, characterized and evaluated as a nanocarrier for the cationic anticancer drug doxorubicin hydrochloride (DOX·HCl). The complex self-assembled into nanorods in aqueous solutions via electrostatic interactions and exhibited a superior drug loading content (50.8%) and drug loading efficiency (90.2%). The average major axis of the drug-loaded nanorods was approximately 300nm, as determined by transmission electron microscopy. An in vitro release assay showed that drug-loaded nanorods exhibited pH-sensitivity and sustained release. Haemolysis assays demonstrated that the polypeptide was haemocompatible, and the polypeptide drug carrier significantly reduced the haemolysis ratio of DOX·HCl. The pharmacokinetics study showed that DOX-loaded nanorods significantly prolonged the resident time in blood. An in vitro cytotoxicity study and cellular uptake assays demonstrated that the DOX-loaded nanorods resulted in higher cell proliferation inhibition and a higher level of tumour cell uptake in A549 cells than with free DOX·HCl. The prolonged circulation and enhanced antitumor efficacy of DOX-loaded nanorods shows promise for efficient cancer chemotherapy.
authors.affiliation: School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China. Electronic address: longerjourney@163.com.
authors.forename: Longlong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China. Electronic address: 794094583@qq.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Hospital of Traditional Chinese Medicine of Jimo, Shandong Province, PR China. Electronic address: qingdaozqy@126.com.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China. Electronic address: zhangyile2001@163.com.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jining First People's Hospital, Shandong Province, PR China. Electronic address: clqiao78@163.com.
authors.forename: Longqiao
authors.initials: L
authors.lastname: Cao
authors.affiliation: School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China. Electronic address: yuxialuan@sdu.edu.cn.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Luan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D061986:MCF-7 Cells; D043942:Nanotubes / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D004317:Doxorubicin
keywords: Cancer chemotherapy; Doxorubicin hydrochloride; Electrostatic interaction; Nanorods; mPEG–PGA