title: Enhanced delivery of Paclitaxel using electrostatically-conjugated Herceptin-bearing PEI/PLGA nanoparticles against HER-positive breast cancer cells.
abstract: We have developed a novel nanoparticle delivery system fabricated from polyethylenimine (PEI) and poly(d,l-lactide-co-glycolide) (PLGA), which were able to deliver the chemotherapeutic agent Paclitaxel, while the biomacromolecule Herceptin acted as a targeting ligand that was conjugated onto the surfaces of the nanoparticles via electrostatic interactions. In this study, these electrostatically-conjugated Herceptin-bearing PEI/PLGA nanoparticles (eHER-PPNs) were optimized and employed as vectors to target HER2-positive breast cancer cells. The eHER-PPNs had an average diameter of ∼ 280 nm and a neutral surface charge (1.00 ± 0.73 mV), which remained stable under physiological conditions. The anticancer effects of eHER-PPNs were investigated in HER2-positive BT474 cells and HER2-negative MCF7 cells. The eHER-PPNs showed enhanced cytotoxicity that was dependent on the receptor expression levels and the incubation time. These conjugated nanoparticles deliver Paclitaxel more efficiently (p<0.001) than unmodified PPNs, Herceptin and the combined effects of these two monotherapies. Furthermore, the chemically-conjugated Herceptin-bearing PEI/PLGA nanoparticles (cHER-PPNs) were fabricated as a comparison. The eHER-PPNs exhibited lower cell viability (46.7%) than that of cHER-PPNs (65.1%). The targeting ability of eHER-PPNs was demonstrated through confocal microscopy images and flow cytometry, which showed that eHER-PPNs displayed higher cellular uptake efficiency (p<0.001) in comparison with cHER-PPNs. Therefore, eHER-PPNs could provide promising platforms for the delivery of therapeutic drugs against HER2-positive breast cancers.
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors.forename: Kongtong
authors.initials: K
authors.lastname: Yu
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors.forename: Zunkai
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China. Electronic address: tenglesheng@jlu.edu.cn.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No.2699, Changchun, Jilin Province 130012, China. Electronic address: liyouxin@jlu.edu.cn.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D065546:Drug Liberation; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055672:Static Electricity; D000068878:Trastuzumab / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011094:Polyethyleneimine; D000068878:Trastuzumab; D017239:Paclitaxel
keywords: Electrostatic attraction; Herceptin; Paclitaxel; Polyethylenimine; Targeted delivery