Rational Design of Multifunctional Dendritic Mesoporous Silica Nanoparticles to Load Curcumin and Enhance Efficacy for Breast Cancer Therapy.
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.
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology Tongji University , Shanghai, PR China.
Jiao
J
Wang
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, Queensland 4072, Australia.
Yue
Y
Wang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology Tongji University , Shanghai, PR China.
Qiang
Q
Liu
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology Tongji University , Shanghai, PR China.
Linnan
L
Yang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology Tongji University , Shanghai, PR China.
Rongrong
R
Zhu
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane, Queensland 4072, Australia.
Chengzhong
C
Yu
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology Tongji University , Shanghai, PR China.
Shilong
S
Wang
D000970:Antineoplastic Agents; D001943:Breast Neoplasms; D003474:Curcumin; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles; D019869:Phosphatidylinositol 3-Kinases; D012822:Silicon Dioxide
D000970:Antineoplastic Agents; D004337:Drug Carriers; D012822:Silicon Dioxide; D019869:Phosphatidylinositol 3-Kinases; D003474:Curcumin
breast cancer; curcumin; dendritic mesoporous silica nanoparticles; folic acid; pH-responsive release