High‐Efficient and Dosage‐Controllable Intracellular Cargo Delivery through Electrochemical Metal–Organic Hybrid Nanogates

Abstract

Intracellular cargo delivery plays an important role in fundamental biological research [1] and therapeutic medical applications, [2] ranging from intracellular function analysis, [3] gene encoding for cellular reprogramming, [4] and the inhibition of gene expression inside cells. [5] Cargo delivery requires safe and efficient access to cells and different intracellular locations such as the nucleus and mitochondria due to impermeable outer cell membranes, including small molecules, [6] nucleic acid genes, [7] amino acid proteins, [8] nanosensors, [9] and organelles. [10] Nanostructures are promising candidates for membrane disruption where versatile cargos transport into cells to overcome the impermeable plasma membrane. Silicon nanowires, [11] diamond nanoneedles, [12] carbon nanofibers, [13] and ZnO nanowires [14] have been developed for mechanical needle penetration into living cells for molecular delivery. Although they improved the delivery efficiency, but the cargo delivery is still restricted by some limitations such as small amount of the loaded/released molecules to/from the nanostructure surfaces (dosage/dosage control). Consequently, hollow nanostructures, including silicon, [15] carbon, [16] and Al 2 O 3 [17] nanotubes (NTs), spontaneously penetrated cells with connection to microfluidic channels, which can control molecular flow and subsequent direct delivery into cells through nanostructured ducts. A plasmid DNA, [18] Ca 2þ indicator, [19] fluorescent dye, [20] quantum dot, [21] and protein [22] were delivered into different cell types using the aforementioned methods. For further improvement, the NTs were combined with external forces such as mechanical, [18] electrical, [23] and photothermal poration. [24,25] Among these methods, an NTelectroporation platform is an excellent technique for intracellular delivery, providing improvement in delivery efficiency and dosage controllability. However, the cell viability still remained a problem due to the high voltages requirement of over 1.5 V to create transient pores in the plasma membrane. [26] Furthermore, such high electrical voltage induces problematic intracellular signaling, which is relative to differentiation [27] and reprogramming. [28] Here, we develop metal-organic hybrid NTs that can be inserted into adhesive cells and subsequently deliver versatile

A Hybrid Nanotube Stamp System in Intracellular Protein Delivery for Cancer Treatment and NMR Analytical Techniques

“…The flux values were 0.133 nmol s –1 cm –2 for the 380 nm NTs and 0.219 nmol s –1 cm –2 for the 750 nm NTs. These values were higher than those obtained with LOx enzymes but lower than the results with green fluorescence protein (GFP, 25 kDa) at 0.8 mM . We observed that the protein flow rate through the NTs stamp was more influenced by concentration than by molecular weight relative to the diffusion constant.…”

Hollow Nanomaterials in Advanced Drug Delivery Systems: From Single‐ to Multiple Shells

“…Moreover, hollow nanostructures and electroporation are beneficial for trans‐barrier transportation because they can transport multifunctional loads into adherent cells. [ 176 ] By combining nanoparticles with external forces such as mechanical, electrical, and photothermal perforation, excellent intracellular delivery techniques can be developed to improve delivery efficiency and dose controllability.…”

Responsive Hydrogels Based on Triggered Click Reactions for Liver Cancer

“…[32] Copyright 2021, The Royal Society of Chemistry. Internal stimuli pH-responsive PEG, TEG Inward diffusion [47,100,118,123,126,129] Redox-responsive PEG Inward diffusion [56,136,156] Enzyme-responsive ALG Cross-linking-codependent [14,27,106,124,130,132,158] Electroresponsive PLGA, PEG Inward diffusion [70,146,196] ROS-responsive PEG, PLGA Self-assembled [149,150,160,162,165] External stimuli Thermoresponsive PEG, PLGA In situ formation [7,30,34,42,67,170,171,173,175,17 8,181] Light-responsive PLGA, ALG Self-assembled [9,28,113,183,185] Magnetic-responsive ALG, HA Cross-linking-codependent [29,166,193,194,195] Mechanoresponsive PEG, PCL Inward diffusion [146,148,197,199,200] Ultrasound-responsive PEG Inward diffusion [14,163,201,…”

“…A combination of electroresponsive nanostructures with compound-loaded nanostructures, and electroresponsive nanostructures with electroresponsive compounds can also be used for electroresponsive drug delivery. [157,158] With the use of polyelectrolytes that contain large numbers of ionizable groups, the polymers become responsive to electrical stimulation by shrinking or swelling. We can design an electroresponsive nanocomposite hydrogel to deliver an antitumor drug targeted at specific sites.…”