Intracellular pH-responsive mesoporous hydroxyapatite nanoparticles for targeted release of anticancer drug

RSC Advances Pub Date: 2015-03-26 DOI: 10.1039/C4RA17114D

Abstract

The design and synthesis of multifunctional nanocarriers is becoming a more and more interesting topic, and shows promising potential for clinical applications. Mesoporous hydroxyapatite nanoparticles (MHAPNs) have emerged as one of the most promising drug delivery vehicles due to their excellent performance. Herein, we constructed a novel cell-targeting, pH-sensitive nanocarrier based on MHAPNs for intracellular drug delivery (LA-BSA-CBA-MHAPNs), using lactobionic acid-conjugated bovine serum albumin (LA-BSA) molecules as end-caps, and 4-carboxyphenylboronic (CBA) as intermediate linkers. The constructed LA-BSA-CBA-MHAPNs as drug delivery carriers exhibited good loading capacity and high pH-controlled release efficiency. Under normal physiological conditions (pH 7.4), they showed a slow drug release rate, while under acidic subcellular environments (pH 5.0) the release rate was enhanced dramatically due to the breakage of cyclic ester bonds linkages between LA-BSA and MHAPNs which made the pores open. Furthermore, our study also demonstrated that the incorporation of the targeted group lactose acid played a positive role in enhancing HepG2 cell uptake efficiency in the LA-BSA-CBA-MHAPNs system in comparison to that of MHAPNs. All these results imply that the LA-BSA-CBA-MHAPNs system could play a significant role in constructing pH-responsive, controlled drug delivery systems for clinical therapy.

Graphical abstract: Intracellular pH-responsive mesoporous hydroxyapatite nanoparticles for targeted release of anticancer drug
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