title: Preparation, characterization, and antitumor activity of paclitaxel-loaded folic acid modified and TAT peptide conjugated PEGylated polymeric liposomes.
abstract: Targeting therapy is a promising strategy for enhancing the therapeutic potential of chemotherapeutic agents. In this study, we report the construction of a multifunctional drug delivery system, termed folic acid modified and TAT peptide conjugated PEGylated polymeric liposomes (FA-TATp-PLs), which is originally derived from octadecyl-quaternized lysine modified chitosan and cholesterol. Our data revealed that FA-TATp-PLs have a particle size of about 60 nm with a zeta potential of about 30 mV, a low burst release effect within the first day, a sustained release for the next 14 days in vitro as well as an instant cellular uptake by folate receptor-overexpressing KB human nasopharyngeal carcinoma cells. In vitro cytotoxicity of paclitaxel-loaded FA-TATp-PLs in KB cells was superior to that of Taxol(®). Furthermore, a comparable antitumor efficacy of paclitaxel-loaded FA-TATp-PLs and Taxol(®) was observed at the same doses in murine models bearing nasopharyngeal carcinoma. These results demonstrate that the paclitaxel formulation not only exhibits a higher antitumor activity but also significantly reduces the toxicity and improves the bioavailability as compared to that of free paclitaxel for the treatment of nasopharyngeal carcinoma. Taken together, our findings indicate that paclitaxel-loaded FA-TATp-PLs are a promising nano-sized drug formulation for future cancer therapy.
authors.affiliation: Institute of Nanobiotechnology, School of Materials Science and Engineering, Tianjin University, Tianjin Key Laboratory of Composites and Functional Materials, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Niu
authors.forename: Peiqi
authors.initials: P
authors.lastname: Zhao
authors.forename: Hanjie
authors.initials: H
authors.lastname: Wang
authors.forename: Man
authors.initials: M
authors.lastname: Yu
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Cao
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Chang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D005260:Female; D005434:Flow Cytometry; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008081:Liposomes; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D023041:Xenograft Model Antitumor Assays; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; C497137:tat peptide (47-57), Human immunodeficiency virus 1; D011092:Polyethylene Glycols; D005492:Folic Acid; D017239:Paclitaxel