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Dual-Functionalized Janus Mesoporous Silica Nanoparticles with Active Targeting and Charge Reversal for Synergistic Tumor-Targeting Therapy.

Abstract
Janus nanoparticles with an anisotropic feature concentrated multiple properties on a single carrier, providing synergistic effects. In this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-DMMA) were constructed with a tumor-targeting ligand (hyaluronic acid, HA) modified on the one side and a charge reversal group (2,3-dimethylmaleic anhydride, DMMA) on the other side. The drug release of HA-JMSN/DOX-DMMA was positively correlated with the acidity of the environment. The cytotoxicity and cell uptake of HA-JMSN/DOX-DMMA were superior to the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-DMMA involved the clathrin-mediated endocytosis (HA) and the micropinocytosis (DMMA) at the same time, which indicated that they both participated in the interaction between nanoparticles and tumor cells. After being injected intravenously in mice, the distribution of HA-JMSN/DOX-DMMA in tumor was enhanced significantly. The antitumor therapy study in vivo showed that HA-JMSN/DOX-DMMA inhibited tumor growth and improved the survival rate of tumor-bearing mice effectively. In general, HA-JMSN/DOX-DMMA could take the synergistic effect of active targeting and charge reversal to deliver drug in tumor cells and kill them efficiently, which was a promising antitumor nanodrug.
AuthorsYajun Liu, Rui Dai, Qiuyu Wei, Wenzhe Li, Guang Zhu, Hao Chi, Zhaoming Guo, Li Wang, Changhao Cui, Jianqiang Xu, Kun Ma
JournalACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 11 Issue 47 Pg. 44582-44592 (Nov 27 2019) ISSN: 1944-8252 [Electronic] United States
PMID31682097 (Publication Type: Journal Article)
Chemical References
  • Drug Carriers
  • Silicon Dioxide
  • Doxorubicin
Topics
  • Animals
  • Cell Line, Tumor
  • Doxorubicin (administration & dosage, chemistry)
  • Drug Carriers (chemistry)
  • Drug Delivery Systems (instrumentation, methods)
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Nanoparticles (chemistry)
  • Neoplasms (drug therapy)
  • Silicon Dioxide (chemistry)

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