Biodegradable nanoneedles for localized delivery of nanoparticles in vivo: exploring the biointerface.
Biodegradable nanoneedles for localized delivery of nanoparticles in vivo: exploring the biointerface.
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DOI：
10.1021/acsnano.5b01490
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发表时间：
2015-05-26
期刊：
影响因子：
17.1
通讯作者：
Stevens MM
中科院分区：
文献类型：
--
作者：
Chiappini C;Martinez JO;De Rosa E;Almeida CS;Tasciotti E;Stevens MM
纳米针通过直接进入细胞质，在介导药物和生物制品的传递以及细胞内传感和单细胞刺激方面显示出潜力。纳米针能够通过细胞膜和内溶体系统进行胞液输送，从而克服了纳米疗法疗效的这些主要障碍。纳米针的低毒和最小侵入性具有在体内持续非免疫原性传递有效载荷的潜力，前提是实现了具有简单部署策略的生物兼容纳米针的开发。在这里，我们提出了一种介孔硅纳米针阵列，它实现了与细胞的紧密接口，快速通过局部生物屏障，在对细胞活力影响最小的情况下暂时进入胞浆。这种紧密的界面既可以在体内传递细胞无关的量子点，也可以在细胞内实时检测pH。随着时间的推移，对生物界面的解剖阐明了细胞结合和纳米针生物降解的动力学，显示了快速界面导致在体外不到30分钟内胞浆有效载荷的输送。在体内将纳米针快速而简单地应用于不同结构的组织表面，总是导致量子点局部地传递到表面细胞，并延长它们的滞留时间。这项研究提供了对纳米针生物界面和传递的动力学的理解，概述了在活组织中高度局部地在细胞内传递纳米颗粒和细胞无关有效载荷的策略。
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 has a potential for the sustained non-immunogenic 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.