The construction of elastin-like polypeptides and their applications in drug delivery system and tissue repair.

Elastin-like polypeptides (ELPs) are thermally responsive biopolymers derived from natural elastin. These peptides have a low critical solution temperature phase behavior and can be used to prepare stimuli-responsive biomaterials. Through genetic engineering, biomaterials prepared from ELPs can have unique and customizable properties. By adjusting the amino acid sequence and length of ELPs, nanostructures, such as micelles and nanofibers, can be formed. Correspondingly, ELPs have been used for improving the stability and prolonging drug-release time. Furthermore, ELPs have widespread use in tissue repair due to their biocompatibility and biodegradability. Here, this review summarizes the basic property composition of ELPs and the methods for modulating their phase transition properties, discusses the application of drug delivery system and tissue repair and clarifies the current challenges and future directions of ELPs in applications.

Gold nanoparticles-decorated peptide hydrogel for antifouling electrochemical dopamine determination.

A reliable and brief ultralow fouling electrochemical sensing system capable of monitoring targets in complex biological media was constructed and validated based on gold nanoparticles-peptide hydrogel-modified screen-printed electrode. The self-assembled zwitterionic peptide hydrogel was prepared by a newly designed peptide sequence of Phe-Phe-Cys-Cys-(Glu-Lys)3 with the N-terminal modified with a fluorene methoxycarbonyl group. The thiol groups on cysteine of the designed peptide are able to self-assemble with AuNPs to form a three-dimensional nanonetwork structure, which showed satisfactory antifouling capability in complex biological media (human serum). The developed gold nanoparticles-peptide hydrogel-based electrochemical sensing platform displayed notably sensing properties for dopamine determination, with a wide linear range (from 0.2 nM to 1.9 µM), a low limit of detection (0.12 nM), and an excellent selectivity. This highly sensitive and ultralow fouling electrochemical sensor was fabricated via simple preparation with concise components that avoid the accumulation of layers with single functional material and complex activation processes. This ultralow fouling and highly sensitive strategy based on the gold nanoparticles-peptide hydrogel with a three-dimensional nanonetwork offers a solution to the current situation of various low-fouling sensing systems facing impaired sensitivity and provides a potential path for the practical application of electrochemical sensors.

Antifouling Strategies for Selective In Vitro and In Vivo Sensing.

The ability to fabricate sensory systems capable of highly selective operation in complex fluid will undoubtedly underpin key future developments in healthcare. However, the abundance of (bio)molecules in these samples can significantly impede performance at the transducing interface where nonspecific adsorption (fouling) can both block specific signal (reducing sensitivity) and greatly reduce assay specificity. Herein, we aim to provide a comprehensive review discussing concepts and recent advances in the construction of antifouling sensors that are, through the use of chemical, physical, or biological engineering, capable of operating in complex sample matrix (e.g., serum). We specifically highlight a range of molecular approaches to the construction of solid sensory interfaces (planar and nanoparticulate) and their characterization and performance in diverse in vitro and in vivo analyte (e.g., proteins, nucleic acids, cells, neuronal transmitters) detection applications via derived selective optical or electrochemical strategies. We specifically highlight those sensors that are capable of detection in complex media or those based on novel architectures/approaches. Finally, we provide perspectives on future developments in this rapidly evolving field.

Free-standing electrochemical biosensor for carcinoembryonic antigen detection based on highly stable and flexible conducting polypyrrole nanocomposite.

A flexible free-standing electrochemical biosensor to detect carcinoembryonic antigen (CEA) is described based on a conducting polypyrrole (PPy) nanocomposite film electrode. The conducting PPy composite was constructed by the sandwiched structure formed by PPy doped with pentaerythritol ethoxylate (PEE) and 2-naphthalene sulfonate (2-NS-PPy) separately via electropolymerization. Gold nanoparticles (AuNPs) were fixed on the PPy composite film by electrodeposition and then connected to CEA aptamer through self-assembly to construct a free-standing electrochemical biosensor breaking away from additional soft substrates and current collector. This PPy composite film-based electrochemical biosensor exhibits satisfying sensing performance for CEA detection, with a linear range from 10-10 g/mL to 10-6 g/mL and a detection limit of 0.033 ng/mL, good specificity and long-term sensing stability (96.8% of the original signal after 15 days). The biosensor also presents acceptable reproducibility with 1.7% relative standard deviation. Moreover, this electrochemical biosensor owns the deformation stability that could bear various deformations (twisting, folding, and knotting) without affecting device's sensing performance. It can even maintain 99.4% of the original signal under 25% strain deformation. Due to the superior sensing performance, high stability (mechanical deformation and long-term storage), and flexibility, this free-standing electrochemical biosensor proves huge potential in application of flexible and wearable electronics.

Electrochemical Aptasensor for Ultralow Fouling Cancer Cell Quantification in Complex Biological Media Based on Designed Branched Peptides.

The rapid, convenient, and selective assaying of clinical targets directly in complex biological media brings with it the potential to revolutionize diagnostics. One major hurdle to impact is retention of selectivity and a tight control of nonspecific surface interactions or biofouling. We report herein, the construction of an antifouling interface through the covalent attachment of designed branched zwitterionic peptides onto electrodeposited polyaniline film. The antifouling capability of the designed branched peptide significantly outperforms that of the commonly used PEG and linear peptides. The interfaces modified with branched peptides are exceptionally effective in reducing a nonspecific protein and cell adsorption, as verified by electrochemical and fluorescent characterization. The derived sensors with mucin1 protein (MUC1) aptamer as the recognition element detect MUC1-positive MCF-7 breast cancer cells in human serum with high sensitivity and selectivity. The linear response range of the cytosensor for the MCF-7 cell is from 50 to 106 cells/mL, with a limit of detection as low as 20 cells/mL. More importantly, the assaying performances remain unchanged in human serum owing to the presence of branched antifouling peptide, indicating feasibility of the cytosensor for practical cancer cell quantification in complex samples.

Electrochemical sensing interfaces based on hierarchically architectured zwitterionic peptides for ultralow fouling detection of alpha fetoprotein in serum.

Herein, an electrochemical sensing platform based on zwitterionic peptide with a hierarchical structure was constructed for ultralow fouling and highly sensitive protein quantification. Through the combination of CPPPPEKEKEKEK and CPPPPEKEKEK peptides, hierarchical antifouling peptide brushes were formed and exhibited excellent antifouling property, which can be further modified with alpha fetoprotein (AFP) aptamer to achieve highly sensitive detection of AFP. The hierarchical peptide brush-based sensor system achieved an AFP quantification range from 1.0 fg mL-1 to 1.0 ng mL-1, with a very low limit of detection as low as 0.59 fg mL-1. In addition, due to the superior antifouling property of the newly designed hierarchical peptide brushes, the electrochemical biosensor supported the quantification of AFP in solutions with a high concentration of nonspecific proteins without sacrifice in sensitivity. It is worth noting that the constructed antifouling biosensor ensured quantitative recruitment of AFP in clinical serum samples with acceptable accuracy when compared with the commonly used method in the hospital. The strategy of constructing sensing interfaces based on designed hierarchical peptide brushes provided an effective way to develop biosensors with both excellent antifouling capability and high sensitivity.

An electrochemical biosensor for alpha-fetoprotein detection in human serum based on peptides containing isomer D-Amino acids with enhanced stability and antifouling property.

The development of antifouling biosensors capable of detecting biomarkers at low concentrations in complex bio-fluids with many interference components is of great importance in the diagnosis and treatment of diseases. Certain zwitterionic peptides composed of natural L-amino acids have been used for the construction of low fouling biosensors and demonstrated excellent antifouling performances, but they are prone to enzymatic degradation in biological media, such as serum that contains a variety of enzymes. In this work, a novel antifouling peptide with the sequence of cppPPEKEKEkek was designed, and three unnatural D-amino acids were set at both ends of the peptide to enhance its tolerance to enzymatic degradation. An electrochemical biosensor was constructed by coupling the antifouling peptide with a conducting polymer polyaniline (PANI) to achieve accurate detection of alpha-fetoprotein (AFP) in clinical samples. Owing to the presence of the designed peptide with partial D-amino acids (pD-peptide), the biosensing interface showed significantly high antifouling performance and enhanced stability in human serum. Meanwhile, the pD-peptide based biosensor exhibited high sensitivity toward the target AFP, with the linear range from 0.1 fg mL-1 to 1.0 ng mL-1 and the limit of detection of 0.03 fg mL-1 (S/N = 3). This strategy of enhancing the stability (tolerance to enzymolysis) of antifouling peptides in biological samples provided an effective way to develop antifouling biosensors for practical applications.

Antifouling biosensors for reliable protein quantification in serum based on designed all-in-one branched peptides.

Antifouling electrochemical biosensors based on designed all-in-one branched peptides that combine anchoring, doping, antifouling and recognizing functions were constructed to support sensitive and reliable protein quantification in complex serum samples.

High-Performance Piezo-Electrocatalytic Sensing of Ascorbic Acid with Nanostructured Wurtzite Zinc Oxide.

Nanostructured piezoelectric semiconductors offer unprecedented opportunities for high-performance sensing in numerous catalytic processes of biomedical, pharmaceutical, and agricultural interests, leveraging piezocatalysis that enhances the catalytic efficiency with the strain-induced piezoelectric field. Here, a cost-efficient, high-performance piezo-electrocatalytic sensor for detecting l-ascorbic acid (AA), a critical chemical for many organisms, metabolic processes, and medical treatments, is designed and demonstrated. Zinc oxide (ZnO) nanorods and nanosheets are prepared to characterize and compare their efficacy for the piezo-electrocatalysis of AA. The electrocatalytic efficacy of AA is significantly boosted by the piezoelectric polarization induced in the nanostructured semiconducting ZnO catalysts. The charge transfer between the strained ZnO nanostructures and AA is elucidated to reveal the mechanism for the related piezo-electrocatalytic process. The low-temperature synthesis of high-quality ZnO nanostructures allows low-cost, scalable production, and integration directly into wearable electrocatalytic sensors whose performance can be boosted by otherwise wasted mechanical energy from the working environment, for example, human-generated mechanical signals.

Low Fouling Protein Detection in Complex Biological Media Supported by a Designed Multifunctional Peptide.

The construction of sensitive and selective biosensors capable of detecting specific targets in complex biological samples remains a challenge highly relevant to a range of sensor/diagnostic applications. Herein, we have utilized a multifunctional peptide to present an interface that supports the very specific recruitment of targets from serum. The novel peptide sequence designed contains an anchoring domain (CPPPP-), an antifouling domain (-NQNQNQNQDHWRGWVA), and a human immunoglobulin G (IgG) recognition domain (-HWRGWVA), and the whole peptide was designed to be antifouling. These were integrated into polyaniline nanowire arrays in supporting the quantification of IgG (with a limit of detection of 0.26 ng mL-1) in neat serum and real clinical samples. The strategy of utilizing multisegment peptide films to underpin highly selective target recruitment is, of course, readily extended to a broad range of targets for which an affinity sequence can be generated.

Nanomaterial-doped conducting polymers for electrochemical sensors and biosensors.

Nanomaterial-doped conducting polymers represent a unique class of composite materials that synergizes the advantageous features of nanomaterials and organic conductors, and they have been used in many applications such as electrochemical sensors and energy storage devices. Conducting polymers can be controllably synthesized from various monomers, and during the polymerization process, different nanomaterials offering unique physical and chemical properties can be doped into the formed conducting polymer composites. In this review, we focus on recent advances in electrochemical sensors and biosensors based on conducting polymers doped with various nanomaterials, including carbon nanomaterials, metal or metal oxide nanoparticles and quantum dots. Approaches to fabrication of films of these materials are described and sensing applications for different targets are summarized.