title: Biodegradable nanoneedles for localized delivery of nanoparticles in vivo: exploring the biointerface.
abstract: 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.
authors: Department of Materials, Imperial College London, London, SW7 2AZ, UK.
authors: Ciro
authors: C
authors: Chiappini
authors: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors: Jonathan O
authors: JO
authors: Martinez
authors: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors: Enrica
authors: E
authors: De Rosa
authors: Department of Materials, Imperial College London, London, SW7 2AZ, UK.
authors: Carina S
authors: CS
authors: Almeida
authors: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors: Ennio
authors: E
authors: Tasciotti
authors: Department of Materials, Imperial College London, London, SW7 2AZ, UK.|Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.|Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
authors: Molly M
authors: MM
authors: Stevens
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007267:Injections; D007700:Kinetics; D008297:Male; D051379:Mice; D009132:Muscles / Q000166:cytology; D053758:Nanoparticles / Q000737:chemistry*; D016062:Porosity; D045663:Quantum Dots / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D012867:Skin / Q000166:cytology
chemical_list: D004337:Drug Carriers; D012822:Silicon Dioxide
keywords: biointerface; drug delivery; nanomedicine; nanoneedles; pH sensing; porous silicon; quantum dots