An ingenious non-spherical mesoporous silica nanoparticle cargo with curcumin induces mitochondria-mediated apoptosis in breast cancer (MCF-7) cells

Abstract

Curcumin delivery to cancer cells is challenging due to its hydrophobic nature, low bio distribution and low availability. Many nano vehicles suffer from low stability and toxicity, and hence the prerequisite of a non-toxic nano vehicle with effective drug delivery is still being delved. The present study investigates the delivery efficiency of curcumin with non-spherical mesoporous silica nanoparticles (MSNAs). Their mechanism of drug delivery and signalling proteins activated to induce apoptosis was further explored in MCF-7 cells. A non-spherical MSN was synthesised, functionalised with PEI (MSNAP) and analysed its intracellular behaviour. Our result indicates that MSNAP was non-toxic until 20 µg/mL and likely localizes in cytoplasmic vesicles. On contrast, well-known MCM-41P induced autophagosome formation, indicating cellular toxicity. Curcumin was loaded on MSNAP and its effectiveness in inducing cell death was studied in MCF-7 and in MCF-7R cells. Curcumin loading on MSNAP induces better cell death with 30 µM curcumin, better than unbounded curcumin. Western blot analysis suggest, curcumin induce apoptosis through the activation of caspase 9, 6, 12, PARP, CHOP and PTEN. The cell survival protein Akt1 was downregulated by curcumin with and without the nanostructure. Interestingly, cleaved caspase 9 was activated in higher amount in nano-conjugated curcumin compared to the free curcumin. But other ER resident protein like IRE1α, PERK and GRP78 were downregulated indicating curcumin disturbs ER homeostasis. Further, electron microscopic analysis reveled that nanocurcumin induced apoptosis by disrupting mitochondria and nucleus. Our results with doxorubicin resistant MCF-7 cell lines confirm nanodelivery of doxorubicin and curcumin sensitised cells effectively at lesser concentration. Further docking studies of curcumin indicate it interacts with the apoptotic proteins through hydrogen bonding formation and with higher binding energy.

The roles of curcumin in regulating the tumor immunosuppressive microenvironment (Review)

“…Curcumin is hypothesized to mediate tumor cell apoptosis through these exogenous pathways. Synthetic curcumin non-spherical mesoporous silica nanoparticles can increase the carrying capacity and saturability of curcumin (35). In-depth studies have shown that curcumin binds apoptotic proteins, such as caspase-3 (36), phosphatase and tensin homolog deleted from chromosome 10 and poly ADP-ribose polymerase (37), inducing mitochondrial damage and thereby promoting tumor cell apoptosis (35).…”

“…Synthetic curcumin non-spherical mesoporous silica nanoparticles can increase the carrying capacity and saturability of curcumin (35). In-depth studies have shown that curcumin binds apoptotic proteins, such as caspase-3 (36), phosphatase and tensin homolog deleted from chromosome 10 and poly ADP-ribose polymerase (37), inducing mitochondrial damage and thereby promoting tumor cell apoptosis (35). Another synthetic nanomaterial, chitosan nanoparticles loaded with demethoxycurcumin in combination with cisplatin, downregulates the expression levels of thymidine phosphorylase required for DNA self-repairing pyrimidine salvage pathways and induces apoptosis in non-small cell lung cancer (NSCLC) cell lines (38).…”

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

“…Lycorine stimulates mitochondrial-mediated apoptosis by up-regulation of ROCK1 [112]. Taking everything into account, it seems that naturally occurring compounds are able to target mitochondrial function in the induction of apoptosis in cancer cells [113,114].…”

Bioactive Compounds: Multi-Targeting Silver Bullets for Preventing and Treating Breast Cancer

“…Co-delivery of curcumin and doxorubicin using core-shell nanoparticles (NPs) with hydrophobic PLLA core loaded with curcumin (Cur) and hydrophilic heparin shell adsorbing doxorubicin (DOX) exhibits promising results for effective breast tumor inhibition [156]. Various research groups have developed nanoparticles containing curcumin alone or in combination with chemotherapies to enhance therapeutic efficacy and bioavailability [157,158,159]. Development of curcumin-loaded solid nanoparticles (Cur-SLN) [157], non-spherical mesoporous silica nanoparticles (MSNAs) [158], and HER2 aptamer-decorated curcumin-loaded human serum albumin nanoparticle (Apt-HSA/CCM NP) [159] are just few examples of nanoparticle approaches.…”