Cancer Therapeutic Proficiency of Dual-Targeted Mesoporous Silica Nanocomposite Endorses Combination Drug Delivery

Abstract

The cargo-loaded mesoporous silica nanoparticles (MSNs) with convenient surface modification can facilitate the development of the innovative nanodrug system. Herein, the present investigation described the electrostatically self-assembled MSNs as a nanosized drug carrier to realize potent synergistic chemotherapy based on the specificity in targeting cytoplasm and nucleus of tumor cells. In this context, the primarily constructed MSNs were subjected with anticancer drug topotecan (TPT) into its large pores. Then, the selective TAT peptide (a nuclear localization signal peptide) was anchored onto TPT-loaded MSNs (TPT-MSN). Subsequently, the positive surface of TPT-MSN-TAT was capped with negatively charged components, poly(acrylic acid) (PAA)-cRGD peptide and citraconic anhydride (CAH)-metformin (MT), and acted as a smart gatekeeper. Comparatively, PAA-cRGD attached onto MSNs serving as the targeted molecules could upsurge by invasion into cancer cells. Interestingly, the acidic pH of the lysosomal compartment in tumor cells triggers the conjugated CAH from the polymer decorated mesoporous silica (PMS) nanocomposite and could efficiently release MT into the cytoplasm. Consequently, the remaining TPT-MSN-TAT efficiently targets the nucleus and delivers the TPT to improve synergistic chemotherapeutic effects. The precisely released drugs were individually enhanced in the in vitro and in vivo cell killing efficiencies. Thus, the study provides a potential drug delivery podium through combined drugs to realize cancer cell targeting approach.

Mesoporous Silica Nanoparticles for Targeting Subcellular Organelles

“…Murugan C et al developed topotecan-loaded MSNs functionalized with the TAT peptide, to which RGD-functionalized poly(acrylic acid) and citraconic anhydride-metformin were added [ 96 ]. The latter components acted as gatekeepers and as masking agents of the positively charged TAT.…”

Eco-Friendly Formulation of Selenium Nanoparticles and Its Functional Characterization against Breast Cancer and Normal Cells

“…Human MDA-MB-231 breast cancer cells were collected from the National Center for Cell Science, Pune, India and stored in DMEM media enriched with 10% FBS, 1% Lglutamine, 1% penicillin, and 1% streptomycin stock solution, at 37°C and 5% CO 2 . The medium was modified every two days and the cells were transferred by trypsinization prior to confluence [30][31][32].…”

New Advances in In Vivo Applications of Gated Mesoporous Silica as Drug Delivery Nanocarriers

“…Dual targeted (cytosol and nucleus) MSNs able to release two different drugs were prepared by Kannan and co‐workers ( Figure ) . The synthesis started with the functionalization of the external surface of MSNs with aminopropyl moieties and pore loading with TPT.…”