36 research outputs found
Enhanced Resolution of Low Molecular Weight Poly(Ethylene Glycol) in Nanopore Analysis
A design with conjugation of DNA
hairpin structure to the polyÂ(ethylene
glycol) molecule was presented to enhance the temporal resolution
of low molecular weight polyÂ(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 polyÂ(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
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 ÎĽL/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
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
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 ÎĽL/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
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
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
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
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
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
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