Endocytosis‐Enabled Construction of Silica Nanochannels Crossing Living Cell Membrane for Transmembrane Drug Transport

Abstract

Artificial transmembrane channel (ATC) analogs are developed for overcoming biological membrane barriers and realizing transmembrane drug delivery, which are mostly studied within artificial lipid bilayers and thus lacked enough stability in practical applications on living cells. Here, natural endocytosis of silica‐based 1D nanomaterials (nanowires) with an ultrahigh aspect ratio is investigated. Enlightened by partially endocytosed ultralong silica nanowires, ATC that can penetrate living cell membranes for transmembrane transportation of small drug molecules is creatively constructed, resulting in enhanced drug delivery efficacy and decreased the half maximal inhibitory concentration. For the first time, an in‐depth study of the cellular uptake of 1D nanomaterials with ultrahigh aspect ratios (from 10 to 120) into living cells is carried out. Through confocal laser scanning microscopy observation, the endocytosis process of ultralong nanowires, including full uptake of short nanowires and partial uptake of longer nanowires, is clarified. Theoretical simulation is performed to give a fundamental understanding on the endocytosis mechanism of ultralong 1D silica nanowires. The simulation results demonstrate the time‐dependent internalization dynamics of the nanowires, which agrees well with our experimental results. This work not only clarifies the cellular interaction between 1D nanomaterials and living cells, but also pioneers the use of natural endocytosis of 1D nanomaterials for constructing ATC.

Enzyme-Powered Tubular Microrobotic Jets as Bioinspired Micropumps for Active Transmembrane Drug Transport

“…We previously demonstrated endocytosisenabled construction of transmembrane channels by using nanosized silica tubes. 6 Hereby, microsized silica tubes were cocultured with living HeLa cells to build the artificial transmembrane channels through endocytosis. It was found that the cells could hardly internalize SMT-2, probably due to the larger size of tubes.…”

“…To date, several kinds of transmembrane channels have been built by partially “inserting” peptide, , carbon, silica or supramolecular nanotubes , into cell membranes. Similar to the biological counterparts, these artificial channels mainly take charge of the substance exchange between the extracellular and intracellular ends, including water molecules, , protons, ionic species, , drug molecules, and even genes .…”

Nanosized Janus AuNR-Pt Motor for Enhancing NIR-II Photoacoustic Imaging of Deep Tumor and Pt2+ Ion-Based Chemotherapy

“…Multifunctional nanomaterials have been developed and widely used in a variety of biological applications, especially in precise tumor imaging and therapy, , showing great potential for accurate diagnosis and treatment of cancer . However, the complex tumor microenvironment displays an uneven distribution of a vascular network, cell membrane barrier, high interstitial pressure, and dense tumor tissue among other factors . These hinder the penetration of passive nanomaterials into deeper tumor tissues, resulting in uneven distribution and less enrichment of nanomaterials in the tumor .…”

“…3 However, the complex tumor microenvironment displays an uneven distribution of a vascular network, cell membrane barrier, high interstitial pressure, and dense tumor tissue among other factors. 4 These hinder the penetration of passive nanomaterials into deeper tumor tissues, resulting in uneven distribution and less enrichment of nanomaterials in the tumor. 5 Recent studies showed that the passive accumulation dose of nanoparticles in tumor tissue is very limited.…”

Ultrasound-augmented anti-inflammatory exosomes for targeted therapy in rheumatoid arthritis

“…[18][19][20][21] Thus, developing more reliable and promising systems for RA treatment is highly urgent but challenging. Recently, it was found that macrophage-derived exosomes featuring good histocompatibility and low immunogenicity can be homed or targeted to inflammatory tissues or cells, 22 and they have been developed as therapeutic agents in many inflammatory or injury models, [23][24][25] for example significantly attenuating the severity of dextran sulfate sodium-induced colitis in mice, 24 attenuating thermal hyperalgesia in a murine model of inflammatory pain, 25 and activating the c-Jun/AP-1 signaling pathway in vascular smooth muscle cell dedifferentiation and vascular tissue repair processes. 26 However, the insufficient anti-inflammatory abilities and intrinsic off-target effects of these exosomes often result in unsatisfactory treatment effects, which remains a challenge in the treatment of RA or other inflammatory diseases.…”