title: Systemic delivery of micelles loading with paclitaxel using N-succinyl-palmitoyl-chitosan decorated with cRGDyK peptide to inhibit non-small-cell lung cancer.
abstract: This study aimed to prepare efficient cRGDyK peptide-decorated micelles for the targeted therapy of non-small-cell lung cancer (NSCLC). An amphiphilic copolymer N-succinyl-palmitoyl-chitosan (SPCS) was synthesized and characterized. cRGDyK peptide is a ligand that can target tumors via specific binding integrin receptor overexpressed on tumor neovascularization and cells. cRGDyK-functionalized SPCS micelles loaded with paclitaxel (PTX/cRGDyK-SPCS) were prepared by film dispersion method and then characterized according to morphology, size, and zeta potential. PTX/cRGDyK-SPCS micelles presented pH-triggered drug release behavior under acidic conditions. The accumulation of micelles detected by laser confocal fluorescence microscopy and flow cytometry showed that cRGDyK-SPCS micelles were easily taken up by A549 cells marked with the luciferase gene (luc-A549). Meanwhile, co-localization of the micelles and lysosomes was recorded dynamically using a live cell station. MTT assays and cell apoptosis studies revealed that cell viability was significantly inhibited by PTX/cRGDyK-SPCS micelles. More importantly, in vivo animal studies showed that cRGDyK-SPCS micelles mainly accumulated in the orthotopic tumor site. PTX/cRGDyK-SPCS micelles exhibited better anti-tumor activity in subcutaneous and orthotopic lung tumors compared with PTX/SPCS micelles and Taxol(®). These results suggested that PTX/cRGDyK-SPCS micelles had better cancer targeting capacity and superior anti-tumor efficacy. Thus, these micelles have great potential as novel carriers in delivering anti-tumor drugs.
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: Yuan
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Ji-zhao
authors.initials: JZ
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Wei-liang
authors.initials: WL
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Shu-di
authors.initials: SD
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Chun-ge
authors.initials: CG
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Zhu
authors.affiliation: College of Radiological Medicine and Protection, Soochow University, Suzhou 215123, People's Republic of China; Changshu Hospital of Traditional Chinese Medicine, Changshu 215500, People's Republic of China.
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Zhou
authors.affiliation: The hospital of Suzhou People's Hospital affiliated to Nanjing Medical University, Suzhou 215000, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China. Electronic address: zhangxuenong@163.com.
authors.forename: Xue-nong
authors.initials: XN
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008819:Mice, Nude; D008823:Micelles; D008870:Microtubules / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D010456:Peptides, Cyclic; C550210:cyclo(Arg-Gly-Asp-Tyr-Lys); D048271:Chitosan; D017239:Paclitaxel
keywords: Keywords: Chitosan; Micelles; Orthotopic lung tumor; cRGDyK; luc-A549