Self‐Powered Intracellular Drug Delivery by a Biomechanical Energy‐Driven Triboelectric Nanogenerator

Nondestructive, high‐efficiency, and on‐demand intracellular drug/biomacromolecule delivery for therapeutic purposes remains a great challenge. Herein, a biomechanical‐energy‐powered triboelectric nanogenerator (TENG)‐driven electroporation system is developed for intracellular drug delivery with high efficiency and minimal cell damage in vitro and in vivo. In the integrated system, a self‐powered TENG as a stable voltage pulse source triggers the increase of plasma membrane potential and membrane permeability. Cooperatively, the silicon nanoneedle‐array electrode minimizes cellular damage during electroporation via enhancing the localized electrical field at the nanoneedle–cell interface and also decreases plasma membrane fluidity for the enhancement of molecular influx. The integrated system achieves efficient delivery of exogenous materials (small molecules, macromolecules, and siRNA) into different types of cells, including hard‐to‐transfect primary cells, with delivery efficiency up to 90% and cell viability over 94%. Through simple finger friction or hand slapping of the wearable TENGs, it successfully realizes a transdermal biomolecule delivery with an over threefold depth enhancement in mice. This integrated and self‐powered system for active electroporation drug delivery shows great prospect for self‐tuning drug delivery and wearable medicine.     

Targeted Liposome‐Loaded Microbubbles for Cell‐Specific Ultrasound‐Triggered Drug Delivery

One of the main problems in cancer treatment is disease relapse through metastatic colonization, which is caused by circulating tumor cells (CTCs). This work reports on liposome‐loaded microbubbles targeted to N‐cadherin, a cell–cell adhesion molecule expressed by CTCs. It is shown that such microbubbles can indeed bind to N‐cadherin at the surface of HMB2 cells. Interestingly, in a mixture of cells with and without N‐cadherin expression, binding of the liposome‐loaded microbubbles mainly occurs to the N‐cadherin‐expressing cells. Importantly, applying ultrasound results in the intracellular delivery of a model drug (loaded in the liposomes) in the N‐cadherin‐expressing cells only. As described in this paper, such liposome‐loaded microbubbles may find application as theranostics and in devices aimed for the specific killing of CTCs in blood.     

A Size‐Selective Intracellular Delivery Platform

Identifying and separating a subpopulation of cells from a heterogeneous mixture are essential elements of biological research. Current approaches require detailed knowledge of unique cell surface properties of the target cell population. A method is described that exploits size differences of cells to facilitate selective intracellular delivery using a high throughput microfluidic device. Cells traversing a constriction within this device undergo a transient disruption of the cell membrane that allows for cytoplasmic delivery of cargo. Unique constriction widths allow for optimization of delivery to cells of different sizes. For example, a 4 μm wide constriction is effective for delivery of cargo to primary human T‐cells that have an average diameter of 6.7 μm. In contrast, a 6 or 7 μm wide constriction is best for large pancreatic cancer cell lines BxPc3 (10.8 μm) and PANC‐1 (12.3 μm). These small differences in cell diameter are sufficient to allow for selective delivery of cargo to pancreatic cancer cells within a heterogeneous mixture containing T‐cells. The application of this approach is demonstrated by selectively delivering dextran‐conjugated fluorophores to circulating tumor cells in patient blood allowing for their subsequent isolation and genomic characterization.     

Drug delivery: Layer‐By‐Layer‐Assembled Capsules and Films for Therapeutic Delivery (Small 17/2010)

Polymeric materials formed via layer‐by‐layer (LbL) assembly have promise for use as drug delivery vehicles. These multilayered materials, both as capsules and thin films, can encapsulate a high payload of toxic or sensitive drugs, and can be readily engineered and functionalized with specific properties. This review highlights important and recent studies that advance the use of LbL‐assembled materials as therapeutic devices. It also seeks to identify areas that require additional investigation for future development of the field. A variety of drug‐loading methods and delivery routes are discussed. The biological barriers to successful delivery are identified, and possible solutions to these problems are discussed. Finally, state‐of‐the‐art degradation and cargo release mechanisms are also presented.     

A Dual‐Responsive Mesoporous Silica Nanoparticle for Tumor‐Triggered Targeting Drug Delivery

A novel pH‐ and redox‐ dual‐responsive tumor‐triggered targeting mesoporous silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC is anchored on the surface of mesoporous silica nanoparticles via disulfide bonds, which are redox‐responsive, as a gatekeeper as well as a tumor‐targeting ligand. PEGylated technology is employed to protect the anchored peptide ligands. The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic‐imine bond, which is pH‐sensitive, are then connected via “click” chemistry to obtain TTTMSN. In vitro cell research demonstrates that the targeting property of TTTMSN is switched off in normal tissues with neutral pH condition, and switched on in tumor tissues with acidic pH condition after removing the MPEG segment by hydrolysis of benzoic‐imine bond under acidic conditions. After deshielding of the MPEG segment, the drug‐loaded nanoparticles are easily taken up by tumor cells due to the exposed peptide targeting ligand, and subsequently the redox signal glutathione in tumor cells induces rapid drug release intracellularly after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery system has great potential for cancer therapy.     

Capturing “Extraordinary” Soft‐Assembled Charge‐Like Polypeptides as a Strategy for Nanocarrier Design

The rational design of nanomedicines is a challenging task given the complex architectures required for the construction of nanosized carriers with embedded therapeutic properties and the complex interface of these materials with the biological environment. Herein, an unexpected charge‐like attraction mechanism of self‐assembly for star‐shaped polyglutamates in nonsalty aqueous solutions is identified, which matches the ubiquitous “ordinary–extraordinary” phenomenon previously described by physicists. For the first time, a bottom‐up methodology for the stabilization of these nanosized soft‐assembled star‐shaped polyglutamates is also described, enabling the translation of theoretical research into nanomaterials with applicability within the drug‐delivery field. Covalent capture of these labile assemblies provides access to unprecedented architectures to be used as nanocarriers. The enhanced in vitro and in vivo properties of these novel nanoconstructs as drug‐delivery systems highlight the potential of this approach for tumor‐localized as well as lymphotropic delivery.