Abstract

Functionalized nanoplatforms show great promise in effectively delivering therapeutics to tumor sites with enhanced permeability and retention effect. Particularly, periodic mesoporous organosilica nanoparticles (PMONs) have become attractive nanocarriers in biomedical applications owing to their large specific surface area and tunable mesoporous channels. In the current work, innovative PMONs with double hybridization of both disulfide and tetrasulfide bonds were synthesized for improved biodegradability and biocompatibility. The constructed PMONs were applied to simultaneously encapsulate aloe-emodin and IR820 (denoted as Aloe-emodin/IR820@PMONs-PEG) for synergistic chemo-photothermal antitumor therapy. Incorporated thioether bonds endowed Aloe-emodin/IR820@PMONs-PEG with GSH-responsive biodegradation behavior, resulting in the controlled release of therapeutics in the tumor-reducing microenvironment. Furthermore, the as-prepared nanocomposites showed great biocompatibility, good photothermal conversion efficiency, and enhanced cellular uptake. The comprehensive in vitro and in vivo assessments exhibited that Aloe-emodin/IR820@PMONs-PEG had a satisfying synergistic chemo-photothermal antitumor effect. In short, this paper provides valuable insights into the rational design of periodic mesoporous organosilica nanoparticles for synergistic antitumor therapy.