Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Research Center for Applied Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
ACS Appl Mater Interfaces. 2020 Sep 23;12(38):42472-42484. doi: 10.1021/acsami.0c07917. Epub 2020 Sep 9.
Nanoparticle (NP)-based targeted drug delivery is intended to transport therapeutically active molecules to specific cells and particular intracellular compartments. However, there is limited knowledge regarding the complete route of NPs in this targeting scenario. In this study, simultaneously performing motion and dynamic pH sensing using single-particle tracking (SPT) leads to an alternative method of gaining insights into the mesoporous silica nanoparticle's (MSN) journey in targeting lysosome. Two different pH-sensitive dyes and a reference dye are incorporated into mesoporous silica nanoparticles (MSNs) co-condensation to broaden the measurable pH range (pH 4-7.5) of the nanoprobe. The phosphonate, amine, and lysosomal sorting peptides (YQRLGC) are conjugated onto the MSN's surface to study intracellular nano-biointeractions of two oppositely charged and lysosome-targetable MSNs. The brightness and stability of these MSNs allow their movement and dynamic pH evolution during their journey to be simultaneously monitored in real time. Importantly, a multidimensional analysis of MSN's movement and local pH has revealed new model intracellular dynamic states and distributions of MSNs, previously inaccessible when using single parameters alone. A key result is that YQRLGC-conjugated MSNs took an alternative route to target lysosomes apart from the traditional one, which sped up to 4 h and enhanced their targeting efficiency (up to 32%). The findings enrich our understanding of the intracellular journey of MSNs. This study offers complementary information on correlating the surface design with the full pathway of nanoparticles to achieve targeted delivery of therapeutic payload.
基于纳米颗粒（NP）的靶向药物输送旨在将治疗活性分子输送到特定的细胞和特定的细胞内隔室。然而，在这种靶向情况下，对于 NPs 的完整途径知之甚少。在这项研究中，通过使用单粒子跟踪（SPT）同时进行运动和动态 pH 传感，为深入了解介孔硅纳米颗粒（MSN）在靶向溶酶体中的旅程提供了一种替代方法。两种不同的 pH 敏感染料和一种参考染料被掺入介孔硅纳米颗粒（MSNs）共缩合中，以拓宽纳米探针的可测量 pH 范围（pH 4-7.5）。膦酸酯、胺和溶酶体分拣肽（YQRLGC）被接枝到 MSN 的表面上，以研究两种带相反电荷且可靶向溶酶体的 MSN 的细胞内纳米生物相互作用。这些 MSN 的亮度和稳定性允许在实时监测它们在旅程中的运动和动态 pH 演化的同时，对它们的运动和动态 pH 演化进行同步监测。重要的是，MSN 的运动和局部 pH 的多维分析揭示了新的模型细胞内动态状态和 MSN 的分布，这在单独使用单个参数时是无法获得的。一个关键的结果是，与传统途径相比，YQRLGC 接枝的 MSN 采用了替代途径来靶向溶酶体，这一途径加速了 4 小时，并提高了它们的靶向效率（高达 32%）。这些发现丰富了我们对 MSN 细胞内旅程的理解。本研究提供了关于表面设计与纳米颗粒完整途径相关的补充信息，以实现治疗有效载荷的靶向递药。
