Enhancing camptothecin loading and release control through physical surface modification of organosilica nanoparticles with polyethylene glycol

The surface modification of nanoparticles holds the potential to enhance the loading capacity of drug molecules and regulate their release, making it possible to exploit the differences between tumor and normal cells. To this end, the surfaces of tetrasulfide-based phenylene-containing biodegradable periodic mesoporous organosilica (BPMO) nanoparticles (designated P4S) are modified herein with a hydrophilic and biocompatible polyethylene glycol (PEG) polymer. The PEG coating is optimized by adjusting the PEG concentration during synthesis, thus resulting in a significant increase in the nanoparticle stability. Furthermore, PEG modification enhances the nanoparticles' camptothecin (CPT) loading capacity. Drug release assessments under physical and acidic pH conditions demonstrate the pH-responsive properties of the P4S nanoparticles upon PEG functionalization, which results in increased drug release at low pH, along with enhanced cellular uptake potential. Notably, the cytotoxicity of CPT against HepG2 cancer cells is significantly improved when loaded into the P4S-PEG nano- particles. These findings reveal the efficacy of PEG surface modification of the drug-delivery material in augmenting the activity of CPT, with promising prospects for clinical applications.