title: Silica nanorattle-doxorubicin-anchored mesenchymal stem cells for tumor-tropic therapy.
abstract: Low targeting efficiency is one of the biggest limitations for nanoparticulate drug delivery system-based cancer therapy. In this study, an efficient approach for tumor-targeted drug delivery was developed with mesenchymal stem cells as the targeting vehicle and a silica nanorattle as the drug carrier. A silica nanorattle-doxorubicin drug delivery system was efficiently anchored to mesenchymal stem cells (MSCs) by specific antibody-antigen recognitions at the cytomembrane interface without any cell preconditioning. Up to 1500 nanoparticles were uploaded to each MSC cell with high cell viability and tumor-tropic ability. The intracellular retention time of the silica nanorattle was no less than 48 h, which is sufficient for cell-directed tumor-tropic delivery. In vivo experiments proved that the burdened MSCs can track down the U251 glioma tumor cells more efficiently and deliver doxorubicin with wider distribution and longer retention lifetime in tumor tissues compared with free DOX and silica nanorattle-encapsulated DOX. The increased and prolonged DOX intratumoral distribution further contributed to significantly enhanced tumor-cell apoptosis. This strategy has potential to be developed as a robust and generalizable method for targeted tumor therapy with high efficiency and low systematic toxicity.
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Guan
authors.forename: Huiyu
authors.initials: H
authors.lastname: Liu
authors.forename: Nanjing
authors.initials: N
authors.lastname: Hao
authors.forename: Tianlong
authors.initials: T
authors.lastname: Liu
authors.forename: Xianwei
authors.initials: X
authors.lastname: Meng
authors.forename: Changhui
authors.initials: C
authors.lastname: Fu
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Li
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Qu
authors.forename: Yingge
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shangyi
authors.initials: S
authors.lastname: Ji
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Fangqiong
authors.initials: F
authors.lastname: Tang
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D059630:Mesenchymal Stem Cells; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012822:Silicon Dioxide; D004317:Doxorubicin