Poly(amino acid)/ZnO/mesoporous silica nanoparticle based complex drug delivery system with a charge-reversal property for cancer therapy

[Display omitted] •A poly(amino acid)/ZnO/MSN based drug delivery system was developed.•Negative charged surface avoided the unspecific uptake by normal cells.•Charge-reversal property promote the endocytosis of carriers at weakly acidic pH.•Dissolution of ZnO intracellular led to DOX release to kill the cancer cells. Negative-to-positive charge-reversal strategy employed in anti-cancer drug delivery systems (DDSs) can improve the utilization of the drugs as well as reduce their side effects efficiently. In this article, a complex DDS named DOX@MSN-ZnO-PLL-PLL(DMA) was prepared. Doxorubicin hydrochloride (DOX) was loaded in mesoporous silica nanoparticles (MSNs), which were then covered by ZnO in situ. Poly-L-lysine (PLL) and 2,3-dimethylmaleic anhydride functionalized PLL (PLL(DMA)) were finally coated on the nanoparticles through a Layer-by-Layer (LbL) assembly process with PLL(DMA) outside to obtain the carriers. The negative charged PLL(DMA) avoided the unspecific uptake of the carriers by normal cells at pH 7.4. While the charge-reversal property could reverse the zeta-potential of the carriers to positive in weakly acidic tumor tissues at pH 6.5, which promoted the cytophagy of the carriers by cancer cells. ZnO which blocked the pores of MSNs could be dissolved intracellular due to the more acidic environment in endosome/lysosome, and resulting in drug release for cancer cell apoptosis. Zeta-potential measurements, the in vitro cellular uptake behaviors as well as cellular cytotoxicity of the carriers at different pH values were investigated to prove the charge-reversal property. The in vitro drug release studies and the cellular cytotoxicity studies were also investigated to prove the controlled DOX release behavior of the carriers. In summary, the complex DDS with charge-reversal property should be of consideration in cancer therapy.