Toxicity-attenuated mesoporous silica Schiff-base bonded anticancer drug complexes for chemotherapy of drug resistant cancer

• Aldehyde-modified mesoporous silica SBA-15-bonded anticancer drug of DOX is synthesised. • CHO-SBA-15/DOX with acid-sensitive Schiff base bonds shows a pH-responsive release of drugs. • The formed CHO-SBA-15/DOX composites show attenuated systemic toxicity. • The CHO-SBA-15/DOX composites hold potential to deal with drug-resistant cancer. Multidrug resistance (MDR), evoked by improper chemotherapeutic practices, poses a serious threat to public health, which leads to increased medical burdens and weakened curative effects. Taking advantage of the enhanced pharmaceutical effect of Schiff base compounds, an aldehyde-modified mesoporous silica SBA-15 (CHO-SBA-15)-bonded anticancer drug combined with doxorubicin hydrochloride (DOX) was synthesized via a Schiff base reaction. Due to the acid-sensitive imine bonds formed between CHO-SBA-15 and DOX, the as-prepared nanocomposites exhibited pH-responsive drug releasing behaviours, resulting in a more enhanced cytotoxic effect on DOX-resistant tumour cells than that of free drugs. Notably, the in vivo studies indicated that mice treated with CHO-SBA-15/DOX composites evidently showed more attenuated systemic toxicity than the free drug molecules. The siliceous mesopore Schiff base-bonded anticancer drug nanocomposite, with minimal chemical modifications, provides a simplified yet efficient therapeutic nanoplatform to deal with drug-resistant cancer.