多模态介孔硅纳米载体用于双重刺激响应药物释放和优异的癌细胞光热消融。

BACKGROUND: Core-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 METHODS: We 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. RESULTS: Magnetic mesoporous silica nanoparticles was prepared by coating a FeO 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/cm). 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. CONCLUSION: Along 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.

背景：开发了具有多模态功能的核壳型介孔硅纳米粒子（MSNs）用于生物成像、与外部 pH 值相关的控制药物释放以及近红外辐射（NIR）刺激、靶向和有效的化学-光热治疗。

材料与方法：我们合成并开发了一种核壳型介孔硅纳米载体用于荧光成像、刺激响应药物释放、磁分离、抗体靶向和化学-光热治疗。此外，还系统研究了基于 FS3 的这些纳米载体的生物相容性、细胞摄取、细胞毒性和光热治疗。

结果：通过在 FeO 核上包覆介孔硅壳，然后接枝荧光化合物，制备了磁性介孔硅纳米粒子，称为 FS3。所得 FM3 预载有治疗性顺铂，并包覆聚多巴胺层，称为 FS3P/C。最终，氧化石墨烯包裹的 FS3P/C（FS3P-G/C）表现出在双刺激（pH、NIR）响应控制释放行为中的高灵敏度。另一方面，Au NPs 包覆的 FS3P/C（FS3P-A/C）表现出更稳定的释放行为，与 pH 变化无关，并且在相同的 NIR 照射下表现出更高的释放速率。值得注意的是，FS3P-A/C 表现出很强的 NIR 吸收，使其能够通过化学-光热治疗效果在 NIR 照射（808nm，1.5W/cm）下破坏 HeLa 细胞。通过共聚焦激光扫描显微镜、流式细胞术和透射电子显微镜仪器获得的图像证实了 FS3 基纳米载体在包括 HeLa（美国模式培养物集存库-ATCC）和 SHSY5Y（ATCC 2266）在内的癌细胞系中的选择性摄取。无顺铂的 FS3 基纳米载体对癌细胞 HeLa 和 SH-SY5Y 表现出良好的细胞摄取和低细胞毒性，但对正常 HEK293（ATCC 1573）细胞没有明显毒性。

结论：随着 FS3 基纳米载体的简便合成，将所有这些策略集成到一个单元中，将成为生物医学应用的有前途的候选者，特别是在化学-光热治疗、靶向递送和针对多种癌细胞类型的刺激响应控制药物释放方面。