Photo-induced reactions for disassembling of coloaded photosensitizer and drug molecules from upconversion-mesoporous silica nanoparticles: An effective synergistic cancer therapy

Abstract

Photodynamic therapy is an emerging noninvasive cancer treatment approach, which requires a photosensitizer (PS), light, and molecular oxygen. In this study, we have successfully fabricated a dual nature (pH- and reactive-oxygen-species-responsive) upconversion nanoparticles (UCNPs) to utilize coloaded doxorubicin (DOX) and chlorin e6 (Ce6) with high antitumor efficacy. The model anticancer drug (DOX) and PS (Ce6) were conjugated in a ratio of 1:1 (w:w), and then loaded on the surface of UCNPs@mesoporous silica (mSiO₂) (85.63 ± 9.87 nm). Cellular uptake could be achieved by either increased permeability or ionic effect of UCNPs@mSiO₂, where Ce6 controlled the DOX release under a near-infrared (NIR) laser irradiation at 980 nm. A cytotoxicity analysis revealed that the dual-responsive UCNPs@mSiO₂ could successfully deliver DOX and Ce6 at the tumor site, causing cell death with a high efficiency. This study shows that the modified UCNPs@mSiO₂ is a promising system to realize NIR-light-triggered PS and drug delivery approach to improve synergistic therapies in vitro and in vivo, in the future.

Keywords: Cancer diagnosis; Drug delivery; Reactive-oxygen-species-responsive; Upconversion nanoparticle; pH-responsive.