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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.
AuthorsZhong Luo, Xingwei Ding, Yan Hu, Shaojue Wu, Yang Xiang, Yongfei Zeng, Beilu Zhang, Hong Yan, Huacheng Zhang, Liangliang Zhu, Junjie Liu, Jinghua Li, Kaiyong Cai, Yanli Zhao
JournalACS nano (ACS Nano) Vol. 7 Issue 11 Pg. 10271-84 (Nov 26 2013) ISSN: 1936-086X [Electronic] United States
PMID24127723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Biocompatible Materials
  • Drug Carriers
  • Silicon Dioxide
  • Doxorubicin
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage)
  • Apoptosis
  • Biocompatible Materials (chemistry)
  • Doxorubicin (administration & dosage)
  • Drug Carriers
  • Endocytosis
  • Endothelial Cells (cytology)
  • HeLa Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Nude
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Nanoparticles (chemistry)
  • Nanotechnology (methods)
  • Neoplasms (metabolism)
  • Neoplasms, Experimental (drug therapy)
  • Oxidation-Reduction
  • Silicon Dioxide (chemistry)

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