title: Engineering a hollow nanocontainer platform with multifunctional molecular machines for tumor-targeted therapy in vitro and in vivo.
abstract: In order to selectively target malignant cells and eliminate severe side effects of conventional chemotherapy, biocompatible and redox-responsive hollow nanocontainers with tumor specificity were fabricated. The mechanized nanocontainers were achieved by anchoring mechanically interlocked molecules, i.e., [2]rotaxanes, onto the orifices of hollow mesoporous silica nanoparticles via disulfide bonds as intermediate linkers for intracellular glutathione-triggered drug release. The [2]rotaxane employed was mainly composed of U.S. Food and Drug Administration approved tetraethylene glycol chains, α-cyclodextrin, and folic acid. In this study, folate groups on the mechanized hollow nanocontainers act as both the tumor-targeting agents and stoppers of the [2]rotaxanes. Detailed investigations showed that anticancer drug doxorubicin loaded mechanized nanocontainers could selectively induce the apoptosis and death of tumor cells. The drug-loaded nanocontainers enhanced the targeting capability to tumor tissues in vitro and inhibited the tumor growth with minimal side effects in vivo. The present controlled and targeted drug delivery system paves the way for developing the next generation of nanotherapeutics toward efficient cancer treatment.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, Singapore 637371.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Luo
authors.forename: Xingwei
authors.initials: X
authors.lastname: Ding
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Shaojue
authors.initials: S
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Zeng
authors.forename: Beilu
authors.initials: B
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.forename: Huacheng
authors.initials: H
authors.lastname: Zhang
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhu
authors.forename: Junjie
authors.initials: J
authors.lastname: Liu
authors.forename: Jinghua
authors.initials: J
authors.lastname: Li
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Cai
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D004705:Endocytosis; D042783:Endothelial Cells / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010084:Oxidation-Reduction; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D012822:Silicon Dioxide; D004317:Doxorubicin