Guanidine–Curcumin Complex-Loaded Amine-Functionalised Hollow Mesoporous Silica Nanoparticles for Breast Cancer Therapy

Abstract

The current study focuses on developing a tumour-targeted functionalised nanocarrier that wraps hollow mesoporous silica nanoparticles. The guanidine carbonate and curcumin are immobilised on the surface of 3-aminopropyl-triethoxy silane (APTES)-decorated hollow mesoporous silica nanoparticles (HMSNP), as confirmed through XPS and NMR analysis. XPS analysis demonstrates that the shape of the hysteresis loops is modified and that pore volume and pore diameter are consequently decreased compared to control. Guanidine (85%) and guanidine–curcumin complex (90%) were successfully encapsulated in HMSNAP and showed a 90% effective and sustained release at pH 7.4 for up to 72 h. Acridine orange/ethidium bromide dual staining determined that GuC-HMNSAP induced more late apoptosis and necrosis at 48 and 72 h compared with Gu-HMNSAP-treated cells. Molecular investigation of guanidine-mediated apoptosis was analysed using western blotting. It was found that cleaved caspases, c-PARP, and GSK-3β (Ser9) had increased activity in MCF-7 cells. GuC-HMSNAP increased the activity of phosphorylation of oncogenic proteins such as Akt (Ser473), c-Raf (Ser249), PDK1 (Ser241), PTEN (Ser380), and GSK-3β (Ser9), thus inducing cell death in MCF-7 cells. Altogether, our findings confirm that GuC-HMNSAP induces cell death by precisely associating with tumour-suppressing proteins, which may lead to new therapeutic approaches for breast cancer therapy.

Exploring the co‐activity of FDA approved drug gemcitabine and docetaxel for enhanced anti‐breast cancer activity: DFT, docking, molecular dynamics simulation and pharmacophore studies

“…The CCC bond angle was theoretically reported as 113.79° and experimentally as 112.8°. These reported parameters have been similar to the optimized structure of gemcitabine and docetaxel complex, that confirms that the structural features of GEDT were in the reported range [43].…”

“…It has been found that the enzymes Poly-ADP-ribose polymerase 1 (PARP-1) and PARP-2, which are more active during the cell cycle's S phase and have larger functions in DNA repair than previously believed, play a role in DNA repair and are known as DNA damage sensors. PARP inhibitors are involved in a semi-targeted therapy for ovarian and breast cancers linked to BRCA1 and BRCA2 [14,15]. By serving as a convergent vehicle for protein interaction, BRCA1 is thought to mediate the function of these proteins in DNA repair, transcriptional transactivation, and cell cycle control [16].…”

Atomic-Level Insights into Hollow Silica-Based Materials for Drug Delivery: Effects of Wettability and Porosity

“…Zhang et al also used hollow silica particles to deliver drugs to enhance therapeutic efficacy. Other applications of hollow silica nanoparticles in drug releasing, such as gated hybrid materials, , biocompatibility , and so forth, − are not shown here. The details can be found in the review literature …”

Curcumin-loaded mesoporous silica nanoparticles for drug delivery: synthesis, biological assays and therapeutic potential – a review

“…Based on docking studies, guanidine-Cur complex clearly targets tumorsuppressing proteins in MCF-7 cells through hydrogen bonding and electrostatic interactions with lower binding affinity, leading to apoptosis. 131 Recently, the antimicrobial effects of Cur-loaded MSNs were evaluated against clinically isolated Porphyromonas gingivalis, which is the main cause of periodontal disease. According to the ndings, P. gingivalis was sensitive to the Cur-loaded MSNs at concentrations of 50-6.25 mg mL −1 with the greatest inhibition zone (p # 0.05) at the concentration of 50 mg mL −1 .…”