Multifunctional hybrid silica nanoparticles for controlled doxorubicin loading and release with thermal and pH dual response

Abstract

Controlled drug loading and release into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to resistance and inefficient cellular uptake. Here, a temperature and pH dual responsive PNiPAM/AA@SiO₂ core–shell particles with internal controlled release were designed and fabricated for efficient cancer treatment, which could recognize the intrinsic pH differences between cancers and normal tissues. Upon lowering the temperature, doxorubicin was loaded into the PNiPAM/AA@SiO₂ nanoparticles, whereas by increasing the acidity, previously loaded doxorubicin was quickly released. Comparing with common mesoporous silica particles (MSNs), these core–shell particles have a more uniform size and better dispersity. In addition, dried PNiPAM/AA@SiO₂ nanoparticles could be easily redispersed in distilled water. The in vitro cell culture experiments showed that not only were PNiPAM/AA@SiO₂ particles more biocompatible and less cytotoxic than MSN, but also DOX@PNiPAM/AA@SiO₂ had a higher drug release efficiency in the lysosomes and a stronger inhibitory effect on tumor cell growth than DOX@MSN. All these features indicated that PNiPAM/AA@SiO₂ particles have great potential in therapy applications.