Abstract
In cancer therapy, controlled and targeted drug release systems are essential to maximize therapeutic outcomes while minimizing adverse effects. This study introduces an innovative mesoporous silicon nanoparticle (MSN) platform, functionalized with the natural anticancer agent dieckol (Di) and designed for precise drug delivery activated by near-infrared (NIR) irradiation. By embedding Di and grafting fluorescent organic conjugates onto the MSN surface, this innovative nanocarrier demonstrates exceptional sensitivity to NIR stimuli and potent chemo-photothermal effects. Notably, drug release remains stable across different pH conditions (7.4, 6.5, and 5.5), ensuring consistent therapeutic delivery. However, upon NIR exposure, the release can be selectively accelerated, enabling precise, real-time, and on-demand drug release control for enhanced treatment efficacy. Cytotoxicity tests revealed that IPSi-Dox-Di-DQA nanoparticles exhibited potent dose-dependent inhibition of cancer cell growth (SH-SY5Y and B16-F10), while sparing healthy cells (HEK-293), highlighting their specificity. Furthermore, advanced 3D cell viability assays mimic the complexities of in vivo cancer environments, with spheroid disintegration under nanoparticle treatment underscoring the platform's powerful anticancer potential. These findings position IPSi-Dox-Di-DQA nanoparticles as a promising frontier in the development of selective, effective cancer therapeutics through synergistic NIR-controlled drug release and mitochondrial targeting.