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

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.

Curcumin-loaded redox-responsive mesoporous silica nanoparticles for targeted breast cancer therapy

“…Here, we analyzed the cell-cycle distribution of MDA-MB-231 and LO2 cells, incubated with free CUR and nanoparticles (MSN/CUR, MSN/ CUR-PEI, MSN/CUR-PEI-FA and MSN/CUR-HA) at 10 lg/mL for 24 h, using propidium iodide staining and flow cytometry ( Figure 10). Free CUR and MSN/CUR induced the G2/M phase cell cycle arrest, as previously reported [25,38]. MSN/CUR-HA and MSN/CUR-PEI-FA also affected the cell-cycle distribution of MDA-MB-231 cells, with the latter showing a greater effect.…”

“…The folate receptor is a tumour-associated protein overexpressed in more than 40% of human tumours, including breast cancer [23,24]. CUR-loaded dendritic MSN modified with folic acid (FA) showed a good dispersion in aqueous solutions and were effectively targeted to MCF-7 human breast cancer cells [25]. We developed a polyethyleneimine (PEI)-FA complex conjugated with MSN via disulphide bonds.…”

Supercritical carbon dioxide-developed silk fibroin nanoplatform for smart colon cancer therapy

“…Reports on cancer therapy in recent years have revealed that CM can cause apoptosis signals in various cancers. [23][24][25] As shown in Figure 5B and D, cells treated with CM-SF NPs showed a higher percentage of apoptosis (~23%) than those treated with 5-Fu (~16%). This indicates that CM-SF NPs had better apoptotic cell-induction potential than 5-Fu.…”

Dendritic Fibrous Nanosilica for Catalysis, Energy Harvesting, Carbon Dioxide Mitigation, Drug Delivery, and Sensing

“…The Ayurvedic drug curcumin (Cur) was also effectively loaded on DFNS, named dendritic mesoporous silica nanoparticles (DMSNs) . Curcumin derived from turmeric has been used daily in India for thousands of years and was first cultivated in Harappa as early as approximately 3000 B.C.…”