介孔有机硅为载体的纳米递送系统制备及其体外化疗-光热联合治疗性能研究

有机/无机杂化的介孔有机硅纳米颗粒因其高的比表面积、丰富的介孔孔道、功能性的骨架以及高的药物装载量等特点而在生物医学领域受到广泛关注。本研究提出以二硫键桥接的有机/无机杂化介孔有机硅纳米颗粒为载体共装载化疗药物和光热剂, 设计制备以DNA分子作为控释“开关”修饰介孔有机硅纳米颗粒的纳米递送系统(ICG/DOX-MONs @DNA₂₀)。该纳米递送系统结合了光热剂的光热效应以及DNA分子随温度升高而从颗粒表面脱附的特性, 可实现近红外光照射激发药物在肿瘤细胞中的控制释放, 同时获得药物化疗-光热联合治疗肿瘤的效果。实验结果表明, 纳米递送系统在近红外光照下能迅速升温至43 ℃以上的热疗温度, 而且在37 ℃条件下6 h内仅缓慢释放药物12.3%, 而当温度升至43 ℃时则快速释放药物52.4%; 细胞实验显示该纳米递送系统能够被HeLa肿瘤细胞吞噬, 在近红外光照下有明显的药物化疗-光热联合治疗效果。因此, ICG/DOX-MONs@DNA₂₀纳米递送系统在药物化疗-光热联合治疗肿瘤方面具有应用前景。

Preparation of Mesoporous Organosilica-based Nanosystem for in vitro Synergistic Chemo- and Photothermal Therapy

Organic-inorganic hybrid mesoporous organosilica has gained more attention in biomedicine due to its high surface area, mesoporous channels, functional framework, and high drug loading capacity. In this study, disulfide- bridged hybrid mesoporous organosilica nanoparticles (MONs) as nanocarriers were employed to construct a nanosystem (ICG/DOX-MONs@DNA₂₀) for delivering drugs and photothermal agents, in which DNA molecules as “switches” were modified on the surface of MONs to control drug release. The results showed that the ICG/DOX-MONs@DNA₂₀ nanosystem could increase the temperature to above 43 ℃ for photothermal therapy with near-infrared (NIR) laser irradiation. On the other hand, the ICG/DOX-MONs@DNA₂₀ nanosystem exhibited a very slow release of DOX (12.3% in 6 h) at 37 ℃, but a rapid release of DOX (52.4% in 6 h) occurred at 43 ℃. Cell culture experiments indicated that the nanosystem can be internalized by HeLa cells, and exhibited an enhanced therapeutic efficacy of synergistic chemo- and photothermal therapy. Hence, the ICG/DOX-MONs@DNA₂₀ nanosystem might be promising for synergistic chemo- and photo-thermal tumor therapy.