MSN anti-cancer nanomedicines: Chemotherapy enhancement, overcoming of drug resistance, and metastasis inhibition

In the anti-cancer war, there are three main obstacles resulting in high mortality and recurrence rate of cancers: the severe toxic side effect of anti-cancer drugs to normal tissues due to the lack of tumor-selectivity, the multi-drug resistance (MDR) to free chemotherapeutic drugs and the deadly metastases of cancer cells. The development of state-of-art nanomedicines based on mesoporous silica nanoparticles (MSNs) is expected to overcome the above three main obstacles. In the view of the fast development of anti-cancer strategy, this review highlights the most recent advances of MSN anti-cancer nanomedicines in enhancing chemotherapeutic efficacy, overcoming the MDR and inhibiting metastasis. Furthermore, we give an outlook of the future development of MSNs-based anti-cancer nanomedicines, and propose several innovative and forward-looking anti-cancer strategies, including tumor tissue-cell-nuclear successionally targeted drug delivery strategy, tumor cell-selective nuclear-targeted drug delivery strategy, multi-targeting and multi-drug strategy, chemo-/radio-/photodynamic-/ultrasound-/thermo-combined multi-modal therapy by virtue of functionalized hollow/rattle-structured MSNs. Anti-cancer nanomedicine: mesoporous silica nanoparticle (MSN) nanomedicines functionalized with targeting, burst responsive, and payload units, as well as a stealth coating, can enhance the chemotherapeutic efficacy and lower toxic side effects by tumor/cell membrane/nuclear-targeted drug delivery and pH/redox/protease- responsive drug release. Moreover, MSN nanomedicines overcome multi-drug resistance by the multi-drug synergy strategy, the effluxcircumventing strategy, and the multimodal combination therapy strategy, and inhibit tumor metastasis.