skip to main content


The NSF Public Access Repository (NSF-PAR) system and access will be unavailable from 5:00 PM ET until 11:00 PM ET on Friday, June 21 due to maintenance. We apologize for the inconvenience.

Title: Electrically Controlled Biochemical Release from Micro/Nanostructures for in vitro and in vivo Applications: A Review

To release biosubstances, including drug molecules, DNAs, and proteins, at prescribed cellular and tissue locations with controllable rates is the Holy Grail of drug delivery that could enable an array of unprecedentedin vitroandin vivoapplications. Extensive research efforts have been focused on exploring innovative mechanisms and approaches for controlling biochemical release with prescribed dose, timing, and dynamics. Particularly, the utilization of electric fields to stimulate the release of biomolecules from synthesized micro/nanostructures has received considerable interest. In this review, we focus on the recent progresses in controlling the release of biomolecules with electric fields by a variety of mechanisms, including electrochemical desorption and actuation, electrically triggered erosion, and electrically driven nanopumps and mechanical motions. The research on external electric stimuli trigged biorelease has progressed rapidly and could make remarkable impact in single‐cell biology, cell‐cell communication, and drug discovery.

more » « less
Award ID(s):
1710922 1150767
Author(s) / Creator(s):
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Page Range / eLocation ID:
p. 1023-1038
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Background

    Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin and azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in the sinuses could mitigate side effects and improve drug concentrations at the infected site. This study was aimed to evaluate the efficacy of the novel ciprofloxacin‐azithromycin sinus stent (CASS) in vitro.


    The CASS was created by coating ciprofloxacin (hydrophilic, inner layer) and azithromycin (hydrophobic, outer layer) onto a biodegradable poly‐l‐lactic acid (PLLA) stent. In‐vitro evaluation included: (1) assessment of drug‐coating stability within the stent using scanning electron microscopy (SEM); (2) determination of ciprofloxacin and azithromycin release kinetics; and (3) assessment of anti‐biofilm activities againstPseudomonas aeruginosa.


    The ciprofloxacin nanoparticle suspension in the inner layer was confirmed by zeta potential. Both ciprofloxacin (60 µg) and azithromycin (3 mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 ± 11.61% of ciprofloxacin and 93.85 ± 6.9% of azithromycin released by 28 days. The CASS also significantly reducedP aeruginosabiofilm mass compared with bare stents and controls (relative optical density units at 590‐nm optical density: CASS, 0.037 ± 0.006; bare stent, 0.911 ± 0.015; control, 1.000 ± 0.000;p< 0.001; n = 3).


    The CASS maintains a uniform coating and sustained delivery of ciprofloxacin and azithromycin, providing anti‐biofilm activities againstP aeruginosa. Further studies evaluating the efficacy of CASS in a preclinical model are planned.

    more » « less
  2. Brennan, Richard Gerald (Ed.)
    ABSTRACT <p>Microbial extracellular proteins and metabolites provide valuable information concerning how microbes adapt to changing environments. In cyanobacteria, dynamic acclimation strategies involve a variety of regulatory mechanisms, being ferric uptake regulator proteins as key players in this process. In the nitrogen-fixing cyanobacterium<italic>Anabaena</italic>sp. strain PCC 7120, FurC (PerR) is a global regulator that modulates the peroxide response and several genes involved in photosynthesis and nitrogen metabolism. To investigate the possible role of FurC in shaping the extracellular environment of<italic>Anabaena</italic>, the analysis of the extracellular metabolites and proteins of a<italic>furC</italic>-overexpressing variant was compared to that of the wild-type strain. There were 96 differentially abundant proteins, 78 of which were found for the first time in the extracellular fraction of<italic>Anabaena</italic>. While these proteins belong to different functional categories, most of them are predicted to be secreted or have a peripheral location. Several stress-related proteins, including PrxA, flavodoxin, and the Dps homolog All1173, accumulated in the exoproteome of<italic>furC</italic>-overexpressing cells, while decreased levels of FurA and a subset of membrane proteins, including several export proteins and<italic>amiC</italic>gene products, responsible for nanopore formation, were detected. Direct repression by FurC of some of those genes, including<italic>amiC1</italic>and<italic>amiC2,</italic>could account for odd septal nanopore formation and impaired intercellular molecular transfer observed in the<italic>furC</italic>-overexpressing variant. Assessment of the exometabolome from both strains revealed the release of two peptidoglycan fragments in<italic>furC</italic>-overexpressing cells, namely 1,6-anhydro-N-acetyl-β-D-muramic acid (anhydroMurNAc) and its associated disaccharide (β-D-GlcNAc-(1-4)-anhydroMurNAc), suggesting alterations in peptidoglycan breakdown and recycling.</p><sec><title>IMPORTANCE

    Cyanobacteria are ubiquitous photosynthetic prokaryotes that can adapt to environmental stresses by modulating their extracellular contents. Measurements of the organization and composition of the extracellular milieu provide useful information about cyanobacterial adaptive processes, which can potentially lead to biomimetic approaches to stabilizing biological systems to adverse conditions.Anabaenasp. strain PCC 7120 is a multicellular, nitrogen-fixing cyanobacterium whose intercellular molecular exchange is mediated by septal junctions that traverse the septal peptidoglycan through nanopores. FurC (PerR) is an essential transcriptional regulator inAnabaena, which modulates the response to several stresses. Here, we show thatfurC-overexpressing cells result in a modified exoproteome and the release of peptidoglycan fragments. Phenotypically, important alterations in nanopore formation and cell-to-cell communication were observed. Our results expand the roles of FurC to the modulation of cell-wall biogenesis and recycling, as well as in intercellular molecular transfer.

    more » « less
  3. Abstract

    Clinical application of injectable, thermoresponsive hydrogels is hindered by lack of degradability and controlled drug release. To overcome these challenges, a family of thermoresponsive, ABC triblock polymer‐based hydrogels has been engineered to degrade and release drug cargo through either oxidative or hydrolytic/enzymatic mechanisms dictated by the “A” block composition. Three ABC triblock copolymers are synthesized with varying “A” blocks, including oxidation‐sensitive poly(propylene sulfide), slow hydrolytically/enzymatically degradable poly(ε‐caprolactone), and fast hydrolytically/enzymatically degradable poly(d,l‐lactide‐co‐glycolide), forming the respective formulations PPS135b‐PDMA152b‐PNIPAAM225(PDN), PCL85b‐PDMA150b‐PNIPAAM150(CDN), and PLGA60b‐PDMA148b‐PNIPAAM152(LGDN). For all three polymers, hydrophilic poly(N,N‐dimethylacrylamide) and thermally responsive poly(N‐isopropylacrylamide) comprise the “B” and “C” blocks, respectively. These copolymers form micelles in aqueous solutions at ambient temperature that can be preloaded with small molecule drugs. These solutions quickly transition into hydrogels upon heating to 37 °C, forming a supra‐assembly of physically crosslinked, drug‐loaded micelles. PDN hydrogels are selectively degraded under oxidative conditions while CDN and LGDN hydrogels are inert to oxidation but show differential rates of hydrolytic/enzymatic decomposition. All three hydrogels are cytocompatible in vitro and in vivo, and drug‐loaded hydrogels demonstrate differential release kinetics in vivo corresponding with their specific degradation mechanism. These collective data highlight the potential cell and drug delivery use of this tunable class of ABC triblock polymer thermogels.

    more » « less
  4. Abstract

    This review summarizes the controllable flow and manipulation of gallium‐based liquid metals (e.g., eutectic gallium indium, EGaIn). There are generally only a few ways to handle fluids, but liquid metals offer versatile control due to their properties: 1) excellent fluidity, 2) adjustable surface tension, 3) electrically and chemically controllable surface oxides, 4) metallic electrical and thermal conductivity, and 5) the ability to alloy with other metals (e.g., magnetic particles). These all‐in‐one properties empower liquid metals to exhibit controllable flow in confined microchannels (steerable flow) and from nozzles (printable flow), and make liquid metals susceptible to various energy fields, including electric, magnetic, electromagnetic, wave, and light fields. Consequently, the flow and manipulation of liquid metals enable intriguing morphological changes (e.g., formation of droplets/plugs, jets, fibers) and controllable motion (e.g., jumping, bouncing, directional locomotion, rotation) of liquid metals with new fluidic phenomena and practical applications such as soft electronics and robotics. This review aims to present a selective framework and provide an insightful understanding for controlling and shaping liquid metals, thereby stimulating further research and generating increased interest in this topic.

    more » « less
  5. Abstract

    Magnetic reconnection in the relativistic regime has been proposed as an important process for the efficient production of nonthermal particles and high-energy emission. Using fully kinetic particle-in-cell simulations, we investigate how the guide-field strength and domain size affect the characteristic spectral features and acceleration processes. We study two stages of acceleration: energization up until the injection energyγinjand further acceleration that generates a power-law spectrum. Stronger guide fields increase the power-law index andγinj, which suppresses acceleration efficiency. These quantities seemingly converge with increasing domain size, suggesting that our findings can be extended to large-scale systems. We find that three distinct mechanisms contribute to acceleration during injection: particle streaming along the parallel electric field, Fermi reflection, and the pickup process. The Fermi and pickup processes, related to the electric field perpendicular to the magnetic field, govern the injection for weak guide fields and larger domains. Meanwhile, parallel electric fields are important for injection in the strong guide-field regime. In the post-injection stage, we find that perpendicular electric fields dominate particle acceleration in the weak guide-field regime, whereas parallel electric fields control acceleration for strong guide fields. These findings will help explain the nonthermal acceleration and emission in high-energy astrophysics, including black hole jets and pulsar wind nebulae.

    more » « less