title: Multifunctional TK-VLPs nanocarrier for tumor-targeted delivery.
abstract: Virus-like particles (VLPs) have been exploited for various biomedical applications, such as the monitoring, prevention, diagnosis and therapy of disease. In this study, a novel multifunctional VLPs nanocarrier (TK-VLPs) was prepared and used for tumor-targeted delivery. The SPR and cell uptake results indicated that the TK peptide is a "bi-functional ligand" with high affinity for Caco-2, HRT-18 and HUVEC cells through the integrin α6β1 and integrin αvβ3 receptors. The results of the direct immunofluorescence, SDS-PAGE and western blot assays demonstrated that the TK-VLPs were successfully prepared using the baculovirus expression system. Confocal laser scanning microscopy and the flow cytometry analysis validated that the TK-VLPs could target to Caco-2, HRT-18 and HUVEC cells. An in vivo study further confirmed that the TK-VLPs could target and efficiently deliver fluorescein to tumor cells and the tumor vasculature in mice bearing subcutaneous tumors. TK-VLPs-DOX displayed a uniform, spherical shape and an average size of approximately 28nm. The results of the cell uptake and cytotoxicity assays indicated that TK-VLPs-DOX could enhance the selectivity for colorectal cancer cells. Together, our studies provide strong evidence that TK-VLPs could target colon tumor cells and tumor angiogenesis with enhanced permeability and retention effects, suggesting that the TK-VLPs are a multifunctional nanocarrier with potential applications in a colon tumor-targeted drug delivery system.
authors.affiliation: Harbin Medical University-Daqing, Daqing 163319, China; Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai 201203, China.
authors.forename: Yachao
authors.initials: Y
authors.lastname: Ren
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine/Community Health Sciences, University of Manitoba, P216-670 Bannatyne Ave, Winnipeg, R3E 0W2 Manitoba, Canada.
authors.forename: Shuman
authors.initials: S
authors.lastname: Yang
authors.affiliation: Da Lian Institute For Drug Control, Dalian 116021, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
authors.forename: Hunan
authors.initials: H
authors.lastname: Sun
authors.affiliation: College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Harbin Medical University-Daqing, Daqing 163319, China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: Peng
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China; College of Animal Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China. Electronic address: zhouyulong1980@163.com.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai 201203, China. Electronic address: wylu@shmu.edu.cn.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D016367:Baculoviridae / Q000235:genetics; D036022:Capsid Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D013937:Thymidine Kinase / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D036022:Capsid Proteins; D004337:Drug Carriers; D010455:Peptides; D011994:Recombinant Proteins; D004317:Doxorubicin; D013937:Thymidine Kinase
keywords: Colonic drug delivery; Nanocarrier; Parvovirus capsid protein VP2; TK peptide; Virus-like particles (VLPs)