Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization

Abstract

The controlled delivery of nucleic acids to selected tissues remains an inefficient process mired by low transfection efficacy, poor scalability because of varying efficiency with cell type and location, and questionable safety as a result of toxicity issues arising from the typical materials and procedures employed. High efficiency and minimal toxicity in vitro has been shown for intracellular delivery of nuclei acids by using nanoneedles, yet extending these characteristics to in vivo delivery has been difficult, as current interfacing strategies rely on complex equipment or active cell internalization through prolonged interfacing. Here, we show that a tunable array of biodegradable nanoneedles fabricated by metal-assisted chemical etching of silicon can access the cytosol to co-deliver DNA and siRNA with an efficiency greater than 90%, and that in vivo the nanoneedles transfect the VEGF-165 gene, inducing sustained neovascularization and a localized sixfold increase in blood perfusion in a target region of the muscle.

Nondestructive nanostraw intracellular sampling for longitudinal cell monitoring

“…1 E and F). Cells grown on the NS demonstrate normal cell behavior and mRNA expression (23,29,33). Previously, we found that NS with a diameter of 100 nm or smaller spontaneously penetrate the cell membrane, allowing the delivery of small molecules into cells.…”

Biodegradable Magnetic Silica@Iron Oxide Nanovectors with Ultra-Large Mesopores for High Protein Loading, Magnetothermal Release, and Delivery

“…[1][2][3][4][5][6][7][8][9][10][11] The absence of particle biodegradability prevents almost always the approval of the food and drug administration (FDA) and other regulatory agencies to enter the pharmaceutical market. Non-degradable nanomaterials are indeed raising concerns of toxicity due to their uncontrolled bio-accumulation.…”

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

“…Over the past decades, several nano-sized DDSs have been developed and applied by targeted drug delivery to cancer cells, such as liposomes, [4][5][6][7] polymeric micelles, [8][9][10][11] dendrimers, [12][13][14][15][16] carbon nanotubes, [17][18][19][20][21][22] inorganic nanoparticles, [23][24][25][26] and silica-based materials. [27][28][29][30][31] Among them, mesoporous silica nanoparticles (MSNs) have attracted much attention due to their unique physiochemical properties, such as large specific surface area and pore volume, controllable particle size, remarkable stability and biocompatibility, and high drug-loading capacity. In 1992, scientists at the Mobil Corporation synthesized ordered mesoporous silica nanomaterials, and this discovery was recognized as a critical breakthrough in material science that could lead to a variety of applications ranging from food manufacturing to pharmaceutical technology.…”