Multimodal Mesoporous Silica Nanocarriers for Dual Stimuli-Responsive Drug Release and Excellent Photothermal Ablation of Cancer Cells.

Abstract

BackgroundCore-shell types of mesoporous silica nanoparticles (MSNs) with multimodal functionalities were developed for bio-imaging, controlled drug release associated with external pH, and near-infrared radiation (NIR) stimuli, and targeted and effective chemo-photothermal therapeutics.Materials and MethodsWe synthesized and developed a core-shell type of mesoporous silica nanocarriers for fluorescent imaging, stimuli-responsive drug release, magnetic separation, antibody targeting, and chemo-photothermal therapeutics. Also, the biocompatibility, cellular uptake, cytotoxicity, and photothermal therapy on these FS3-based nanocarriers were systematically investigated.ResultsMagnetic mesoporous silica nanoparticles was prepared by coating a Fe3O4 core with a mesoporous silica shell, followed by grafting with fluorescent conjugates, so-called FS3. The resulting FM3 was preloaded with therapeutic cisplatin and coated with polydopamine layer, so-called FS3P/C. Eventually, graphene oxide-wrapped FS3P/C (FS3P-G/C) exhibited high sensitivity in the dual stimuli (pH, NIR)-responsive controlled release behavior. On the other hand, Au NPs-coated FS3P/C (FS3P-A/C) exhibited more stable release behavior, irrespective of pH changes, and exhibited much more enhanced release rate under the same NIR irradiation. Notably, FS3P-A/C showed strong NIR absorption, enabling photothermal destruction of HeLa cells by its chemo-photothermal therapeutic effects under NIR irradiation (808 nm, 1.5 W/cm2). The selective uptake of FS3-based nanocarriers was confirmed in cancer cell lines including HeLa (American Type Culture Collection - ATCC) and SHSY5Y (ATCC 2266) by the images obtained from confocal laser scanning microscopy, flow cytometry, and transmission electron microscopy instruments. Cisplatin-free FS3-based nanocarriers revealed good cellular uptake and low cytotoxicity against cancerous HeLa and SH-SY5Y cells, but showed no obvious toxicity to normal HEK293 (ATCC 1573) cell.ConclusionAlong with the facile synthesis of FS3-based nanocarriers, the integration of all these strategies into one single unit will be a prospective candidate for biomedical applications, especially in chemo-photothermal therapeutics, targeted delivery, and stimuli-responsive controlled drug release against multiple cancer cell types.