Size and charge dual-transformable mesoporous nanoassemblies for enhanced drug delivery and tumor penetration.
Size and charge dual-transformable mesoporous nanoassemblies for enhanced drug delivery and tumor penetration.
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DOI：
10.1039/c9sc06260b
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发表时间：
2020-02-03
期刊：
影响因子：
8.4
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Chen L;Zhao T;Zhao M;Wang W;Sun C;Liu L;Li Q;Zhang F;Zhao D;Li X
纳米粒制剂给药过程中的一系列生物屏障不可避免地导致了目前给药效率低、肿瘤穿透受限、药物细胞内化不足等问题。这些多重生物屏障与纳米粒子的物理化学性质密切相关，特别是对于长血液循环(大和负)、肿瘤深入渗透(小)以及有效的细胞内化(正)对大小和表面电荷的矛盾需求。在这里，我们报道了肿瘤微环境触发的大小和电荷双重可转化的纳米组件。纳米组装是通过将正上/下转换发光纳米颗粒(U/DCNPs)固定在大的介孔二氧化硅纳米颗粒(MSN)上，通过不稳定的酸键形成核心@卫星结构的MSN@U/DCNPs纳米组装，然后对电荷可逆聚合物进行封端。在生理pH下，具有较大尺寸(∼180 nm)和负电荷的集成纳米组装件可以有效地延长血液循环和高肿瘤聚集。而在酸性的肿瘤微环境中，MSN和U/DCNPs之间外部聚合物的电荷反转和连接体的断裂可以导致纳米组装的解体，形成孤立的MSN和更小的U/DCNP，两者都带有正电荷，从而增强了肿瘤的穿透和细胞对游离纳米粒子的摄取。结合U/DCNPs独立的近红外(NIR)-可见光和近红外-近红外(NIR-NIR)发光和MSN的高比表面积，纳米组装件具有双重转化能力，可以实现近红外生物成像引导的化疗和光动力学联合治疗，具有显著的抗肿瘤效果。为了克服药物输送系统中的多种生物障碍，开发了尺寸和电荷双重可转换的核心@卫星结构纳米组件。
A series of biological barriers in a nanoparticle-formulated drug delivery process inevitably result in the current low delivery efficiency, limited tumor penetration and insufficient cellular internalization of drugs. These multiple biological barriers are intimately related to the physicochemical properties of nanoparticles, especially the contradictory demand on size and surface charge for long blood circulation (larger and negative) and deep tumor penetration (smaller) as well as efficient cellular internalization (positive). Herein, we report tumor microenvironment triggered size and charge dual-transformable nanoassemblies. The nanoassembly is realized by immobilizing positive up/downconverting luminescent nanoparticles (U/DCNPs) onto large mesoporous silica nanoparticles (MSNs) via acid-labile bonds to form core@satellite structured MSN@U/DCNPs nanoassemblies, and subsequent capping of charge reversible polymers. At physiological pH, the integrated nanoassemblies with a larger size (∼180 nm) and negative charge can effectively achieve a prolonged blood circulation and high tumor accumulation. While under an acidic tumor microenvironment, the charge reversal of outer polymers and cleavage of linkers between MSNs and U/DCNPs can induce disintegration of the nanoassemblies into isolated MSNs and smaller U/DCNPs, both with a positively charged surface, which thereby potentiate the tumor penetration and cell uptake of dissociated nanoparticles. Combined with the independent near-infrared (NIR)-to-visible and NIR-to-NIR luminescence of U/DCNPs and high surface area of MSNs, the nanoassemblies can implement NIR bioimaging guided chemo- and photodynamic combined therapy with remarkable antitumor efficiency because of the high accumulation and deep tumor penetration induced by the dual transformability of the nanoassemblies. Size and charge dual-transformable core@satellite structured nanoassemblies are developed to overcome multiple biological barriers in a drug delivery system.
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