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 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.

Accelerating the Translation of Nanomaterials in Biomedicine

“…47,48 This technology could prove transformative in the fields of drug delivery, regenerative medicine, and biosensing. The dynamics of the nanoneedle entry to the cell and study of the nanoneedle–cell interface have been elucidated and pave the way for highly controlled delivery of a range of nanoparticle payloads intracellularly.…”

“…The dynamics of the nanoneedle entry to the cell and study of the nanoneedle–cell interface have been elucidated and pave the way for highly controlled delivery of a range of nanoparticle payloads intracellularly. 47 Furthermore, the nanoneedle array can simultaneously deliver both DNA and siRNA with high efficiency (over 90%) and in vivo proved successful in upregulating blood vessel formation in muscle by delivery of the VEGF-165 gene (Figure 5C–E). 48 The Stevens group has also developed several other notable nanomaterials-based technologies, particularly enzyme-response nanoparticle systems that have a wide range of important impacts in the field of biosensing.…”

Nanoneedle-Based Sensing in Biological Systems

“…The length, diameter, density and in general the geometry of the needles, their composition, as well as the type of cell and the mechanism of interfacing influence the interaction, ultimately resulting in different mechanisms of access to intracellular information, not all of which are yet clarified. Interfacing occurs either by allowing the cells to adhere and spread over nanoneedles or by forcefully applying the nanoneedles over cells or tissues 3 . In the first instance, cell suspensions are simply dispensed over the nanoneedles, following which the cells are the only active player that determine the evolution of the interfacing with the substrate.…”

“…Applying this strategy to biopsy samples of tumors can distinguishing normal and tumor regions and delineate intracellular Cathepsin B activity across tumor margin samples with resolution approaching that of single cells ( Figure 6D). This same nanoneedle array (Si) can distinguish cancer cells from healthy ones by probing their intracellular pH 3 . Ratiometric measurement of the fluorescence intensity of a pH sensitive dye and a pH insensitive one simultaneously conjugated to the nanoneedles, maps pH across the array ( figure 6E).…”

“…Other notable efforts are those related to measuring intracellular conditions, such as pH 3 , which can provide an overall indication of cell metabolism, and the measurement of cell tension through the force they exert 17 . The signal from this wide variety of targets requires different transduction mechanisms.…”