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ACS Appl Mater Interfaces. 2016 Oct 12;8(40):26511-26523. Epub 2016 Sep 27.

Rational Design of Multifunctional Dendritic Mesoporous Silica Nanoparticles to Load Curcumin and Enhance Efficacy for Breast Cancer Therapy.

Author information

1
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology Tongji University , Shanghai, PR China.
2
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, Queensland 4072, Australia.

Abstract

Breast cancer is the primary reason for cancer-related death in women worldwide and the development of new formulations to treat breast cancer patients is crucial. Curcumin (Cur), a natural product, exerts promising anticancer activities against various cancer types. However, its therapeutic efficacy is hindered as a result of poor water solubility, instability, and low bioavailability. The aim of this work is to assess the curative effect of a novel nanoformulation, i.e., Cur-loaded and calcium-doped dendritic mesoporous silica nanoparticles modified with folic acid (Cur-Ca@DMSNs-FA) for breast cancer therapy. The results manifested that Cur-Ca@DMSNs-FA dispersed very well in aqueous solution, released Cur with a pH-responsible profile, and targeted efficiently to human breast cancer MCF-7 cells. Further investigations indicated that Cur-Ca@DMSNs-FA effectively inhibited cell proliferation, increased intracellular ROS generation, decreased mitochondrial membrane potential, and enhanced cell cycle retardation at G2/M phase, leading to a higher apoptosis rate in MCF-7 compared to free Cur. Moreover, the Western blotting analysis demonstrated that Cur-Ca@DMSNs-FA were more active than free Cur through suppression of PI3K/AKT/mTOR and Wnt/β-catenin signaling, and activation of the mitochondria-mediated apoptosis pathway. In addition, hemolysis assay showed that the Ca@DMSNs-FA exhibited good biocompatibility. Last, in vivo studies indicated that when Cur was encapsulated in Ca@DMSNs-FA, the Cur concentration in blood serum and tumor tissues was increased after 1 h intraperitoneal injection. In conclusion, Cur-Ca@DMSNs-FA might act as a potential anticancer drug formulation for breast cancer therapy.

KEYWORDS:

breast cancer; curcumin; dendritic mesoporous silica nanoparticles; folic acid; pH-responsive release

PMID:
27619078
DOI:
10.1021/acsami.6b08400
[Indexed for MEDLINE]

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