Tailoring chemical compositions of biodegradable mesoporous organosilica nanoparticles for controlled slow release of chemotherapeutic drug

Biodegradable periodic mesoporous organosilica nanoparticles (B-PMO) are an outstanding nanocarrier due to their biodegradability and high drug load capacities. The present study describes a synthesis of a phenylenecontaining tetrasulfide based B-PMO, named P4S. The incorporation of aromatic phenylene groups into the framework creates a strong interaction between nanoparticles (NPs) with aromatic rings in the cordycepin molecules. This results in the low release profile under various conditions. In addition, the replacement of this linker slowed the degradation of nanoparticles. The physicochemical properties of the nanoparticles are evaluated and compared with a biodegradable ethane-containing tetrasulfide based PMO and a non-degradable MCM41. The biodegradability of P4S is also demonstrated in a reducing environment and the 100 nm spherical nanoparticles completely decomposed within 14 days. The porous structure of P4S has a high loading of hydrophilic cordycepin (approximately 731.52 mg g-1) with a slow releasing speed. The release rates of P4S NPs are significantly lower than other materials, such as liposomes, gelatin nanoparticles, and photo-crosslinked hyaluronic acid methacrylate hydrogels, in the same solution. This specific release behavior could guarantee drug therapeutic effects with minimum side-effects and optimized drug dosages. Most importantly, according to the in vitro cytotoxicity study, cordycepin-loaded P4S NPs could retain the toxicity against liver cancer cell (HepG2) while suppressed the cytotoxicity against normal cells (BAEC).

Automated summary

The biodegradable B-PMO nanoparticles, particularly the P4S synthesized in this study, exhibited high drug loading capacity and slow release profile, making it an excellent nanocarrier for therapeutic drugs. The incorporation of aromatic phenylene groups in the framework enhanced the interaction with cordycepin molecules, resulting in specific release behavior and minimal side effects. Moreover, P4S demonstrated complete biodegradability in a reducing environment within 14 days, with high drug loading and slower release compared to conventional materials like liposomes, gelatin nanoparticles, and hydrogels.