Mesoporous silica nanoparticles with surface transformation ability for prostate cancer treatment

Abstract

Prostate cancer is one of most devastating disease with the poor prognosis in men. The efficacy of conventional therapies is far from satisfactory due to the insufficient chemotherapeutic delivery to the cancer cells which requires the extremely high or toxic dose to reach the therapeutic window. In this work, a charge reversal nanoplatform based on mesoporous silica nanoparticle (MSN) with a core-shell structure is developed to programmatically overcome persistent obstacles in drug delivery to prostate cancer. MSN is served as a container to high-efficiently pack chemotherapeutic drug of triptolide. 2, 3-dimethylmaleic anhydride grafted poly-(allylamine hydrochloride) (PAH-DA) is used as the out shell with a negative charge for pH-triggered charge reversal, which can facilitate the cellular uptake. Furthermore, PAH-DA shell can also act as pH-sensitive gatekeepers while will elegantly shed from MSN under acidic tumor microenvironment for controlling drug release. As expected, in vitro cell experiments demonstrated that the as-prepared nanoplatform (denoted as MSN-T@PAH-DA) could be efficiently uptaken by LNCaP prostate cancer cells and exhibited a better anti-cancer effect at pH 6.5 as compared to that at pH 7.4. After intravenous injection, MSN-T@PAH-DA had a relatively higher tumor accumulation than MSN-T@PAH-SA counterpart without charge conversion ability, and thus achieving enhanced tumor growth suppression in mouse model of prostate cancer. Therefore, the pH-response surface charge reversal capacity of PAH-DA shell could enable multitasking in controlling drug release, regulating tumor accumulation and cellular internalization, which provided a promising strategy for efficient prostate tumor treatment.