Department of Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
Faraday Discuss. 2020 Jun 19;222(0):304-317. doi: 10.1039/c9fd00124g.
Developing therapeutic nanoparticles that actively target disease cells or tissues by exploiting the binding specificity of receptors presented on the cell surface has extensively opened up biomedical applications for drug delivery and imaging. An ideal nanoparticle for biomedical applications is required to report confirmation of relevant targeting and the ultimate fate in a physiological environment for further verification, e.g. to adapt dosage or predict response. Herein, we demonstrate tracking of silicon nanoparticles through intrinsic photoluminescence (PL) during the course of cellular targeting and uptake. Time-resolved analysis of PL characteristics in cellular microenvironments provides dynamic information on the physiological conditions where the silicon nanoparticles are exposed. In particular, the PL lifetime of the silicon nanoparticles is in the order of microseconds, which is significantly longer than the nanosecond lifetimes exhibited by fluorescent molecules naturally presented in cells, thus allowing discrimination of the nanoparticles from the cellular background autofluorescence in time-gated imaging. The PL lifetime is a physically intensive property that reports the inherent characteristics of the nanoparticles regardless of surrounding noise. Furthermore, we investigate a unique means to inform the lifespan of the biodegradable silicon nanoparticles responsive to local microenvironment in the course of endocytosis. A multivalent strategy of nanoparticles for enhanced cell targeting is also demonstrated with complementary analysis of time-resolved PL emission imaging and fluorescence correlation spectroscopy. The result presents the promising potential of the photoluminescent silicon nanoparticles toward advanced cell targeting systems that simultaneously enable tracking of cellular trafficking and tissue microenvironment monitoring.
开发治疗性纳米粒子,通过利用细胞表面上呈现的受体的结合特异性主动靶向疾病细胞或组织,为药物输送和成像的生物医学应用开辟了广泛的途径。对于生物医学应用,理想的纳米粒子需要报告相关靶向的确认以及在生理环境中的最终命运,以进一步验证,例如调整剂量或预测反应。在此,我们通过细胞靶向和摄取过程中的固有光致发光(PL)证明了硅纳米粒子的跟踪。细胞微环境中 PL 特征的时间分辨分析提供了有关硅纳米粒子暴露的生理条件的动态信息。特别是,硅纳米粒子的 PL 寿命为数微秒,明显长于细胞中天然存在的荧光分子的纳秒寿命,从而允许在时间门控成像中从细胞背景自发荧光中区分纳米粒子。PL 寿命是一种物理密集型特性,它报告了纳米粒子的固有特性,而与周围噪声无关。此外,我们研究了一种独特的方法,以告知在细胞内吞过程中响应局部微环境的可生物降解硅纳米粒子的寿命。还通过时间分辨 PL 发射成像和荧光相关光谱的互补分析,研究了纳米粒子的多价策略以增强细胞靶向。结果表明,光致发光硅纳米粒子在先进的细胞靶向系统中具有很大的应用潜力,同时能够跟踪细胞迁移和组织微环境监测。