Contribution of carboxyl modified chiral mesoporous silica nanoparticles in delivering doxorubicin hydrochloride in vitro: pH-response controlled release, enhanced drug cellular uptake and cytotoxicity

In this study, dual functionalized mesoporous silica nanoparticle (Dual-MSN) with functions of carboxyl modification and chirality was successfully developed and its special contribution in delivering doxorubicin hydrochloride (DOX) in vitro was mainly studied. Characteristics of Dual-MSN and its application as DOX carrier were intensively explored by comparing with naked non-functionalized MSN (Naked MSN). The results indicated that both Naked MSN and Dual-MSN significantly controlled DOX release due to the release hindrance caused by mesopores. As expected, Dual-MSN exhibited obvious enhanced pH response because of its negative charges of carboxyl groups. DOX loaded Naked MSN and DOX loaded Dual-MSN presented better cytotoxicity than DOX due to carrier-mediated endocytosis and the favorable intercalation of DOX into DNA in the nuclei. The cytotoxicity of DOX loaded Dual-MSN was better than DOX loaded Naked MSN owing to its enhanced cellular uptake induced by chirality of Dual-MSN, demonstrating that double functions of Dual-MSN had unique advantages in improving antitumor effect of DOX towards MCF-7 cells and thus confirming its special contribution in DOX delivery. (C) 2016 Elsevier B.V. All rights reserved.