36 research outputs found

    Enhanced Resolution of Low Molecular Weight Poly(Ethylene Glycol) in Nanopore Analysis

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    A design with conjugation of DNA hairpin structure to the poly­(ethylene glycol) molecule was presented to enhance the temporal resolution of low molecular weight poly­(ethylene glycol) in nanopore studies. By the virtue of this design, detection of an individual PEG with molecular weight as low as 140 Da was achieved at the single-molecule level in solution, which provides a novel strategy for characterization of an individual small molecule within a nanopore. Furthermore, we found that the current duration time of poly­(ethylene glycol) was scaled with the relative molecular weight, which has a potential application in single-molecule detection

    Polypyrrole-Based Implantable Electroactive Pump for Controlled Drug Microinjection

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    Implantable devices for long-lasting controlled insulin microinjection are of great value to diabetic patients. To address this need, we develop a flexible electroactive pump based on a biocompatible polypyrrole composite film that comprises a polypyrrole matrix and a macromolecular dopant of polycaprolactone-<i>block</i>-polytetrahydrofuran-<i>block</i>-polycaprolactone. Using phosphate-buffered saline as the electrolyte, this film demonstrates much higher electroactivity and reproducibility than conventional Cl<sup>–</sup>-doped polypyrrole, making it an excellent actuator for driving an implantable pump. At a driving current density of 1 mA/cm<sup>2</sup>, the pump demonstrates a consistent output capacity of 10.5 at 0.35 μL/s over 20 cycles. This work paves the way for the development of an implantable electroactive pump to improve the quality of life of diabetics

    Bio-Inspired Synthetic Nanovesicles for Glucose-Responsive Release of Insulin

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    A new glucose-responsive formulation for self-regulated insulin delivery was constructed by packing insulin, glucose-specific enzymes into pH-sensitive polymersome-based nanovesicles assembled by a diblock copolymer. Glucose can passively transport across the bilayer membrane of the nanovesicle and be oxidized into gluconic acid by glucose oxidase, thereby causing a decrease in local pH. The acidic microenvironment causes the hydrolysis of the pH sensitive nanovesicle that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies validated that the release of insulin from nanovesicle was effectively correlated with the external glucose concentration. In vivo experiments, in which diabetic mice were subcutaneously administered with the nanovesicles, demonstrate that a single injection of the developed nanovesicle facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 5 days

    Polypyrrole-Based Implantable Electroactive Pump for Controlled Drug Microinjection

    No full text
    Implantable devices for long-lasting controlled insulin microinjection are of great value to diabetic patients. To address this need, we develop a flexible electroactive pump based on a biocompatible polypyrrole composite film that comprises a polypyrrole matrix and a macromolecular dopant of polycaprolactone-<i>block</i>-polytetrahydrofuran-<i>block</i>-polycaprolactone. Using phosphate-buffered saline as the electrolyte, this film demonstrates much higher electroactivity and reproducibility than conventional Cl<sup>–</sup>-doped polypyrrole, making it an excellent actuator for driving an implantable pump. At a driving current density of 1 mA/cm<sup>2</sup>, the pump demonstrates a consistent output capacity of 10.5 at 0.35 μL/s over 20 cycles. This work paves the way for the development of an implantable electroactive pump to improve the quality of life of diabetics

    Analysis of a Single α‑Synuclein Fibrillation by the Interaction with a Protein Nanopore

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    The formation of an α-synuclein fibril is critical in the pathogenesis of Parkinson’s disease. The native unfolded α-synuclein monomer will translocate through an α-hemolysin nanopore by applied potential at physiological conditions in vitro. Applying a potential transformed α-synuclein into a partially folded intermediate, which was monitored by capture inside the vestibule of an α-hemolysin nanopore with a capture current of 20 ± 1.0 pA. The procedure involves the critical early stage of α-synuclein structural transformation. Further elongation of the intermediate produces a block current to 5 ± 0.5 pA. It is revealed that the early stage fibril of α-synuclein inside the nanopore is affected by intrapeptide electrostatic interaction. In addition, trehalose cleared the fibrillation by changing the surface hydrophobic interaction of A53T α-synuclein, which did not show any inhibition effect from WT α-synuclein. The results proved that the interpeptide hydrophobic interactions in the elongation of A53T α-synuclein protofilaments can be greatly weakened by trehalose. This suggests that trehalose inhibits the interpeptide interaction involved in protein secondary structure. The hydrophobic and electrostatic interactions are associated with an increase in α-synuclein fibrillation propensity. This work provides unique insights into the earliest steps of the α-synuclein aggregation pathway and provides the potential basis for the development of drugs that can prevent α-synuclein aggregation at the initial stage

    Accurate Data Process for Nanopore Analysis

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    Data analysis for nanopore experiments remains a fundamental and technological challenge because of the large data volume, the presence of unavoidable noise, and the filtering effect. Here, we present an accurate and robust data process that recognizes the current blockades and enables evaluation of the dwell time and current amplitude through a novel second-order-differential-based calibration method and an integration method, respectively. We applied the developed data process to analyze both generated blockages and experimental data. Compared to the results obtained using the conventional method, those obtained using the new method provided a significant increase in the accuracy of nanopore measurements

    Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody

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    Despite recent advances in melanoma treatment through the use of anti-PD-1 (aPD1) immunotherapy, the efficacy of this method remains to be improved. Here we report an innovative self-degradable microneedle (MN) patch for the sustained delivery of aPD1 in a physiologically controllable manner. The microneedle is composed of biocompatible hyaluronic acid integrated with pH-sensitive dextran nanoparticles (NPs) that encapsulate aPD1 and glucose oxidase (GOx), which converts blood glucose to gluconic acid. The generation of acidic environment promotes the self-dissociation of NPs and subsequently results in the substantial release of aPD1. We find that a single administration of the MN patch induces robust immune responses in a B16F10 mouse melanoma model compared to MN without degradation trigger or intratumoral injection of free aPD1 with the same dose. Moreover, this administration strategy can integrate with other immunomodulators (such as anti-CTLA-4) to achieve combination therapy for enhancing antitumor efficacy

    Drug delivery for fighting infectious diseases: a global perspective

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    Epidemiologists have predicted that viral infections might spread fast in our highly globalized world. For example, a report on “Preparedness for a high-impact respiratory pathogen pandemic” was published in September 2019 by Johns Hopkins Centre for Health Security [1]. This report ranked aerosol transmitted viral diseases as the highest risk for a wide-spreading pandemic and named, as an example beyond infuenza, also severe acute respiratory syndrome (SARS) as a zoonotic coronavirus. In approximately 1 year, SARSCoV-2 (coronavirus type 2) has developed into a true pandemic and reminds is that problems must be taken seriously in a timely manner. In the case of the current coronavirus disease 2019 (COVID-19), we profited from the protocols established during earlier pandemics. Following the infuenza (H1N1) pandemic in 2009, a pandemic preparedness plan was developed by the World Health Organization (WHO). SARS-CoV infections in 2003 and MERS (Middle East Respiratory Syndrome) in 2012 lead to research in this type of Coronaviridae and strategies to combat them. The Ebola epidemic in West Africa 2014–2016 activated a push for programs in preventive and therapeutic strategies driven by governmental and non-governmental institution

    Analysis of a Single α‑Synuclein Fibrillation by the Interaction with a Protein Nanopore

    No full text
    The formation of an α-synuclein fibril is critical in the pathogenesis of Parkinson’s disease. The native unfolded α-synuclein monomer will translocate through an α-hemolysin nanopore by applied potential at physiological conditions in vitro. Applying a potential transformed α-synuclein into a partially folded intermediate, which was monitored by capture inside the vestibule of an α-hemolysin nanopore with a capture current of 20 ± 1.0 pA. The procedure involves the critical early stage of α-synuclein structural transformation. Further elongation of the intermediate produces a block current to 5 ± 0.5 pA. It is revealed that the early stage fibril of α-synuclein inside the nanopore is affected by intrapeptide electrostatic interaction. In addition, trehalose cleared the fibrillation by changing the surface hydrophobic interaction of A53T α-synuclein, which did not show any inhibition effect from WT α-synuclein. The results proved that the interpeptide hydrophobic interactions in the elongation of A53T α-synuclein protofilaments can be greatly weakened by trehalose. This suggests that trehalose inhibits the interpeptide interaction involved in protein secondary structure. The hydrophobic and electrostatic interactions are associated with an increase in α-synuclein fibrillation propensity. This work provides unique insights into the earliest steps of the α-synuclein aggregation pathway and provides the potential basis for the development of drugs that can prevent α-synuclein aggregation at the initial stage

    Analyzing Carbohydrate–Protein Interaction Based on Single Plasmonic Nanoparticle by Conventional Dark Field Microscopy

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    We demonstrated a practical method to analyze carbohydrate–protein interaction based on single plasmonic nanoparticles by conventional dark field microscopy (DFM). Protein concanavalin A (ConA) was modified on large sized gold nanoparticles (AuNPs), and dextran was conjugated on small sized AuNPs. As the interaction between ConA and dextran resulted in two kinds of gold nanoparticles coupled together, which caused coupling of plasmonic oscillations, apparent color changes (from green to yellow) of the single AuNPs were observed through DFM. Then, the color information was instantly transformed into a statistic peak wavelength distribution in less than 1 min by a self-developed statistical program (nanoparticleAnalysis). In addition, the interaction between ConA and dextran was proved with biospecific recognition. This approach is high-throughput and real-time, and is a convenient method to analyze carbohydrate–protein interaction at the single nanoparticle level efficiently
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