Thermo and pH dual responsive, polymer shell coated, magnetic mesoporous silica nanoparticles for controlled drug release

Abstract

In this paper, a kind of core–shell composite microsphere was prepared based on poly(N-isopropylacrylamide-co-methacrylic acid) (P(NIPAM-co-MAA)) coated magnetic mesoporous silica nanoparticles (M-MSN) via precipitation polymerization. The composite microsphere presented a thermo/pH-coupling sensitivity and the volume phase transition could be precisely regulated by the molar ratio of MAA to NIPAM or the concentration of NaCl. At physiological conditions (37 °C, 0.15 M NaCl), the P(NIPAM-co-MAA) shell underwent a distinct transition from a swollen state in pH 7.4 to a collapsed state in pH 5.0, so that the polymer shell was active in moderating the diffusion of embedded drugs in-and-out of the pore channels of MSN. Doxorubicin hydrochloride (DOX) was applied as a model drug and the behaviors of drug storage/release were investigated. The drug loaded behavior was pH-dependent, and the composite microsphere had a drug embed efficiency of about 91.3% under alkaline conditions. The cumulative in vitro release of the DOX-loaded composite microsphere showed a low level of leakage below the volume phase transition temperature (VPTT) and was significantly enhanced above its VPTT, exhibiting an apparent thermo/pH-response controlled drug release. The cytotoxicity assay of a blank carrier to normal cells indicated that the composite microspheres were suitable as drug carriers, while the DOX-loaded composite microspheres had a similar cytotoxicity to HeLa cells compared with free DOX. Therefore, the thermo/pH-sensitive composite microsphere could, in principle, be used for in vivo cancer therapy with a low premature drug release during blood circulation whilst having a rapid release upon reaching tumor tissues.