Chiappini Ciro, Martinez Jonathan O, De Rosa Enrica, Almeida Carina S, Tasciotti Ennio, Stevens Molly M
Department of Materials, Imperial College London, London, SW7 2AZ, UK.
Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
ACS Nano. 2015 May 26;9(5):5500-5509. doi: 10.1021/acsnano.5b01490. Epub 2015 Apr 17.
Nanoneedles display potential in mediating the delivery of drugs and biologicals, as well as intracellular sensing and single-cell stimulation, through direct access to the cell cytoplasm. Nanoneedles enable cytosolic delivery, negotiating the cell membrane and the endolysosomal system, thus overcoming these major obstacles to the efficacy of nanotherapeutics. The low toxicity and minimal invasiveness of nanoneedles have a potential for the sustained nonimmunogenic delivery of payloads in vivo, provided that the development of biocompatible nanoneedles with a simple deployment strategy is achieved. Here we present a mesoporous silicon nanoneedle array that achieves a tight interface with the cell, rapidly negotiating local biological barriers to grant temporary access to the cytosol with minimal impact on cell viability. The tightness of this interfacing enables both delivery of cell-impermeant quantum dots in vivo and live intracellular sensing of pH. Dissecting the biointerface over time elucidated the dynamics of cell association and nanoneedle biodegradation, showing rapid interfacing leading to cytosolic payload delivery within less than 30 minutes in vitro. The rapid and simple application of nanoneedles in vivo to the surface of tissues with different architectures invariably resulted in the localized delivery of quantum dots to the superficial cells and their prolonged retention. This investigation provides an understanding of the dynamics of nanoneedles' biointerface and delivery, outlining a strategy for highly local intracellular delivery of nanoparticles and cell-impermeant payloads within live tissues.
纳米针在介导药物和生物制剂的递送以及细胞内传感和单细胞刺激方面显示出潜力，因为它可以直接进入细胞质。纳米针能够实现胞质递送，穿过细胞膜和内溶酶体系统，从而克服了纳米治疗药物疗效的这些主要障碍。纳米针的低毒性和微创性有可能在体内持续进行非免疫原性的载荷递送，前提是要开发出具有简单部署策略的生物相容性纳米针。在此，我们展示了一种介孔硅纳米针阵列，它能与细胞形成紧密的界面，迅速跨越局部生物屏障，以最小程度影响细胞活力的方式暂时进入细胞质。这种界面的紧密性使得细胞不可渗透的量子点能够在体内递送，并能对细胞内的pH值进行实时传感。随着时间推移剖析生物界面，阐明了细胞结合和纳米针生物降解的动态过程，显示在体外不到30分钟内就能实现快速界面结合并导致胞质载荷递送。纳米针在体内快速、简单地应用于不同结构的组织表面，总是能将量子点局部递送至表层细胞并使其长期保留。这项研究有助于理解纳米针生物界面和递送的动态过程，概述了在活组织内对纳米颗粒和细胞不可渗透的载荷进行高度局部细胞内递送的策略。
