RSM-CCD optimized Hollow Mesoporous Silica Nanospheres encapsulating Sorafenib induces apoptotic cell death in Non-Small Cell Lung Cancer

Abstract

The remarkable drug loading and release potential of hollow mesoporous silica nanoparticles (HMSNs) renders them attractive nanovehicles for drug delivery. We synthesized HMSNs in this work utilizing a unique solvent-extracted technique. ANOVA and a 3-factorial design were used to assess the impact of the independent variables, CTAB (X1), TEOS (X2), and pH (X3). The optimal synthesis formulation was predicted by RSM-CCD as TEOS: 4 ml, pH: 11; CTAB: 0.2 g. XRD, FTIR, TEM, BET, and FE-SEM were used to characterize optimized MSNs and HMSNs. The limited solubility and dose-dependent toxicity of antineoplastic drug sorafenib (SF), however, make it difficult to establish as a standard drug. We developed an SF-encapsulated nanovehicle and investigated its complete anti-tumor activity using A549 cells. SF-MSNs and SF-HMSNs had drug loading efficiencies of 10.71 ± 0.33 % and 41.31 ± 0.94 %, in that sequence. A study on drug dissolution demonstrated the pH-dependent sustainable release of SF, demonstrating the superiority of SF-HMSNs with cumulative release percentages of 65 % (HMSNs) and 78 % (MSNs) at 72 hours at pH - 5. To investigate the potential anti-tumorigenic effects of both free and encapsulated SF, in vitro cell culture experiments were conducted. The MTT assay was utilized to evaluate the cytotoxicity of improved SF-HMSNs against A549 cells, revealing increased toxicity. Furthermore apoptotic cell death in A549 cells was evident because of elevated drug sensitivity and ROS production. These results suggest that HMSNs as the perfect drug delivery system for treating NSCLC because of the sustained release of SF.