PH and Thermo Dual-Stimuli-Responsive Drug Carrier Based on Mesoporous Silica Nanoparticles Encapsulated in a Copolymer–Lipid Bilayer

Abstract

A pH and thermo dual-controllable composite structure was developed as a triggerable drug delivery carrier. In such a drug carrier, a mesoporous silica nanoparticle (MSN) acts as the drug loading core, while a layer of copolymer-lipid serves as the dual-responsive gating shell. Specifically, the copolymer-lipid bilayer consists of natural phospholipids (soy phosphatidylcholine, SPC) and the poly(N-isopropylacrylamide-methacrylic acid-octadecyl acrylate) (p(NIPAM-MAA-ODA)) copolymer. With this structure, a high drug loading capacity and a sustained release effect could be provided by the MSN core, while a pH and thermo dual-responsive releasing ability could be offered by the copolymer-lipid bilayer. In addition, the introduction of SPC instead of the traditionally used phospholipids (such as dioleoyl phosphatidylethanolamine (DOPE) or dipalmitoyl phosphatidylcholine (DPPC)) results in a much lower cost and a better serum stability. Using doxorubicin (DOX) as the drug model, our results confirmed that either pH or temperature can trigger the drug release. However, much more drugs could be released by simultaneously controlling the pH and temperature. Furthermore, after being cocultured with cancer cells (MCF-7), the drug carriers transported DOX into the cells and exhibited a pH-sensitive release behavior. Since most tumor sites usually exhibit a more acidic environment or a higher temperature, the pH- and thermo-responsive releasing ability of this drug carrier is particularly useful and important for the targeted release at the tumor region. Thus, due to the powerful controlled releasing ability, the straightforward preparation method, and low cost, the demonstrated nanocarrier will have potential applications in controllable drug delivery and cancer therapy.