期刊
ACS NANO
卷 9, 期 5, 页码 5500-5509出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b01490
关键词
nanoneedles; porous silicon; drug delivery; nanomedicine; biointerface; pH sensing; quantum dots
类别
资金
- Defense Advanced Research Projects Agency [W911NF-11-0266]
- Department of Defense [W81XWH-12-10414]
- NIH [1R21CA173579-01A1, 5F31CA154119-02]
- UTMDACC Institutional Core Grant [CA16672]
- Newton International Fellowship
- Marie Curie International Incoming Fellowship
- Wellcome Trust
- EPSRC [EP/K020641/1]
- ERC consolidator grant Naturale-CG
- Rosetrees Trust
- EPSRC [EP/K020641/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/K020641/1] Funding Source: researchfish
- Rosetrees Trust [M300-CD1, M300-F1-CD3] Funding Source: researchfish
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.
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