Zwitterionic Peptide Research Articles

Zwitterionic Peptides: From Mechanism, Design Strategies to Applications.

Zwitterionic peptides, as a type of peptide composed of charged residues, are electrically neutral, which combine the advantages of zwitterionic materials and biological peptides, exhibiting hydrophilicity and programmable properties. As attractive candidates for resisting nonspecific adsorption of biomacromolecules and microorganisms, zwitterionic peptides have been applied in materials science, biomedicine, and biochemistry over the past decade. In this review, the development of zwitterionic peptides has been systematically outlined and analyzed, including their mechanisms, structure-function relationships, and design strategies. Furthermore, this review emphasizes and discusses their recent applications for developing functional coatings, biosensors, drug delivery systems, and engineering proteins. Finally, future research perspectives and challenges of zwitterionic peptides are also prospected and discussed. This review is intended to provide clarity and insight into the design and applications of zwitterionic peptides.

Mussel-inspired protein-based nanoparticles for curcumin encapsulation and promoting antitumor efficiency

Curcumin demonstrated therapeutic potential for cancer. However, its medical application is limited due to low solubility, poor stability and low absorption rate. Here, we used the mussel-inspired functional protein (MPKE) to fabricate the curcumin-carrying nanoparticle (Cur-MPKE) for encapsulating and delivering curcumin. The protein MPKE is composed of the mussel module and zwitterionic peptide. The Dopa group bonding characteristic of the mussel module was leveraged for the self-assembly of nanoparticles, while the superhydrophilic property of the zwitterionic peptide was utilized to enhance the stability of nanoparticles. As expected, MPKE and Cur are tightly bound through hydrogen bonds and dynamic imide bonds to form nanoparticles. Cur-MPKE showed improved solubility and stability in aqueous solutions as well as excellent biocompatibility. Besides, Cur-MPKE also exhibited pH-triggered release and enhanced uptake of curcumin by tumor cells, promoting the antioxidant activity and antitumor effect of curcumin. Moreover, systemic experiments of Cur-MPKE to rats demonstrated that Cur-MPKE significantly inhibited tumor tissue growth and proliferation without causing obvious systemic toxicity. This work provides a new strategy for fabricating the delivery system of curcumin with improved stability, sustainability and bioavailability.

Fabrication of an Antifouling Surface Plasmon Resonance Sensor with Stratified Zwitterionic Peptides for Highly Efficient Detection of Peanut Allergens in Biscuits.

Peanut allergen monitoring is currently an effective strategy to avoid allergic diseases, while food matrix interference is a critical challenge during detection. Here, we developed an antifouling surface plasmon resonance sensor (SPR) with stratified zwitterionic peptides, which provides both excellent antifouling and sensing properties. The antifouling performance was measured by the SPR, which showed that stratified peptide coatings showed much better protein resistance, reaching ultralow adsorption levels (<5 ng/cm2). Atomic force microscopy was used to further analyze the antifouling mechanism from a mechanical perspective, which demonstrated lower adsorption forces on hybrid peptide coatings, confirming the better antifouling performance of stratified surfaces. Moreover, the recognition of peanut allergens in biscuits was performed using an SPR with high efficiency and appropriate recovery results (98.2-112%), which verified the feasibility of this assay. Therefore, the fabrication of antifouling sensors with stratified zwitterionic peptides provides an efficient strategy for food safety inspection.

Electrogenerated Chemiluminescence Biosensor for Quantization of Matrix Metalloproteinase-3 in Serum via Target-Induced Cleavage of Oligopeptide

A highly sensitive and selective electrogenerated chemiluminescence (ECL) biosensor was developed for the determination of matrix metalloproteinase 3 (MMP-3) in serum via the target-induced cleavage of an oligopeptide. One ECL probe (named as Ir-peptide) was synthesized by covalently linking a new cyclometalated iridium(III) complex ([(3-pba)2Ir(bpy-COOH)](PF6)) (3-pba = 3-(2-pyridyl) benzaldehyde, bpy-COOH = 4′-methyl-2,2′-bipyridine-4-carboxylic acid) with an oligopeptide (CGVPLSLTMGKGGK). An ECL biosensor was fabricated by firstly casting Nafion and gold nanoparticles (AuNPs) on a glassy carbon electrode and then self-assembling both of the ECL probes, 6-mercapto-1-hexanol and zwitterionic peptide, on the electrode surface, from which the AuNPs could be used to amplify the ECL signal and Ir-peptide could serve as an ECL probe to detect the MMP-3. Thanks to the MMP-3-induced cleavage of the oligopeptide contributing to the decrease in ECL intensity and the amplification of the ECL signal using AuNPs, the ECL biosensor could selectively and sensitively quantify MMP-3 in the concentration range of 10–150 ng·mL−1 and with both a limit of quantification (26.7 ng·mL−1) and a limit of detection (8.0 ng·mL−1) via one-step recognition. In addition, the developed ECL biosensor showed good performance in the quantization of MMP-3 in serum samples, with a recovery of 92.6% ± 2.8%–105.6% ± 5.0%. An increased level of MMP-3 was found in the serum of rheumatoid arthritis patients compared with that of healthy people. This work provides a sensitive and selective biosensing method for the detection of MMP-3 in human serum, which is promising in the identification of patients with rheumatoid arthritis.

Passivating the Background of Living Microbes with a Zwitterionic Peptide for Therapies.

Living microbial therapies have been proposed as a course of action for a variety of diseases. However, problematic interactions between the host immune system and the microbial organism present significant clinical concerns. Previously, we developed a genetically encoded superhydrophilic zwitterionic peptide, termed EKP, to mimic low-immunogenic zwitterionic materials, which have been used for the chemical modification of biologics such as protein and nucleic acid drugs to increase their in vivo circulation time and reduce their immunogenicity. Herein, we demonstrate the protective effects of the EKP polypeptide genetically cloaking the surface of Saccharomyces cerevisiae as a model microbe in both in vitro and in vivo systems. First, we show that EKP peptide cloaking suppresses the interactions between yeast cells and their specific antibodies, thereby illustrating its cloaking behavior. Then, we examine the in vitro interactions between EKP peptide surface cloaked yeast cells and murine macrophage cells, which exhibit phagocytotic behavior in the presence of foreign microbes. Our results indicate that EKP cloaking suppresses macrophage interactions and thus reduces phagocytosis. Furthermore, EKP cloaked yeast cells demonstrate a prolonged circulation time in mice in vivo.

Click Conjugation of Zwitterionic Peptide with DNA Strand: An Efficient Antifouling Strategy for Versatile Photoelectrochemical Aptasensor.

Advanced antifouling biosensors have garnered considerable attention for their potential for precise and sensitive analysis in complex human bodily fluids. Herein, a pioneering approach was utilized to establish a robust and versatile photoelectrochemical aptasensor by conjugating a zwitterionic peptide with a DNA strand. Specifically, the branched zwitterionic peptide (BZP) was efficiently linked to complementary DNA (cDNA) through a click reaction, forming the BZP-cDNA conjugate. This intriguing conjugate exploited the BZP domain to create an antifouling biointerface, while the cDNA component facilitated subsequent hybridization with probe DNA (pDNA). To advance the development of the aptasensor, an upgraded PDA/HOF-101/ZnO ternary photoelectrode was designed as the signal converter for the modification of the BZP-cDNA conjugate, while a bipyridinium (MCEPy) molecule with strong electron-withdrawing properties was labeled at the front end of the pDNA to form the pDNA-MCEPy signal probe. Targeting the model of mucin-1, a remarkable enhancement in the photocurrent signal was achieved through exonuclease-I-aided target recycling. Such an engineered zwitterionic peptide-DNA conjugate surpasses the limitations imposed by conventional peptide-based sensing modes, exhibiting unique advantages such as versatility in design and capability for signal amplification.

Zwitterionic peptide pendant as a homing agent to achieve lymphatic targeting antigen-specific immunotherapy of allergenic protein

Targeting the lymphatic route has gained extensive attention in drug delivery due to its potential to reduce drug dosage and improve therapeutic effects. However, the lack of an effective targeting path limits the development of relevant treatments. Herein, we reported a zwitterionic peptide pendant conjugation strategy to render protein drugs with lymphatic targeting capability, which merited subsequent allergen-specific immunotherapy (AIT). The zwitterionic peptide pendant of alternatively repeated glutamic acid (E) and lysine (K) sequences was conjugated to the causative allergenic protein tropomyosin (TM) through recombinant protein expression. The recombinant TM-EK exhibited a decreased immunogenicity and improved lymphatic targeting efficacy. It was found that the TM-EK could effectively induce the mice to achieve immune tolerance to TM and had no noticeable toxic or side effects on major organs. The proposed zwitterionic peptide strategy provided a new approach to developing lymphatic targeting protein drugs and facilitating the improvement of immunotherapies.

An antifouling coating that enables electrochemical biosensing of MecA gene in complex samples

As an important emerging pollutant, antibiotic resistance genes (ARGs) monitoring is crucial to protect the ecological environment and public health, but its accurate detection is still a major challenge in complex environment samples. In this study, a robust antifouling electrochemical DNA biosensor (E-DNA biosensor) was proposed for highly sensitive and selective detection of the mecA gene in complex water samples. The antifouling coating of electrode consisted of a branched-shaped zwitterionic peptide and gold nanoparticles (CPEK-AuNPs). And, the PPPP linker of peptide between the anchoring and antifouling domains adopted a polyproline helix conformation. The CPEK-AuNPs-modified electrode interface with stable hydration layer prevented non-specific interactions while enhancing electron transfer to the electrode surface, resulting in high current response and outstanding antifouling performance. Coupled with synergistic isothermal strand displacement polymerase reaction (ISDPR), the proposed antifouling sensing strategy exhibited superb sensitivity for the mecA gene. The limit of detection (LOD) was as low as 16.67 fM (S/N = 3) in a broad linear range of 0.05–5000 pM, and a high specificity to resolve from even single base mismatch towards the complex water samples was obtained. Benefiting from the stable hydration layer, the as-prepared E-DNA biosensor preserved 91.8 % of the initial signal after 15 days of exposure in unprocessed wastewater samples. The excellent specificity, stability and reproducibility (RSD＜3%) of mecA gene detection indicated that the proposed sensing strategy with antifouling performance can be a versatile tool for accurate quantitative analysis of ARGs in complex environment samples.

Design, synthesis and structure-activity relationship (SAR) studies of an unusual class of non-cationic fatty amine-tripeptide conjugates as novel synthetic antimicrobial agents.

Cationic ultrashort lipopeptides (USLPs) are promising antimicrobial candidates to combat multidrug-resistant bacteria. Using DICAMs, a newly synthesized family of tripeptides with net charges from -2 to +1 and a fatty amine conjugated to the C-terminus, we demonstrate that anionic and neutral zwitterionic USLPs can possess potent antimicrobial and membrane-disrupting activities against prevalent human pathogens such as Streptococcus pneumoniae and Streptococcus pyogenes. The strongest antimicrobials completely halt bacterial growth at low micromolar concentrations, reduce bacterial survival by several orders of magnitude, and may kill planktonic cells and biofilms. All of them comprise either an anionic or neutral zwitterionic peptide attached to a long fatty amine (16-18 carbon atoms) and show a preference for anionic lipid membranes enriched in phosphatidylglycerol (PG), which excludes electrostatic interactions as the main driving force for DICAM action. Hence, the hydrophobic contacts provided by the long aliphatic chains of their fatty amines are needed for DICAM's membrane insertion, while negative-charge shielding by salt counterions would reduce electrostatic repulsions. Additionally, we show that other components of the bacterial envelope, including the capsular polysaccharide, can influence the microbicidal activity of DICAMs. Several promising candidates with good-to-tolerable therapeutic ratios are identified as potential agents against S. pneumoniae and S. pyogenes. Structural characteristics that determine the preference for a specific pathogen or decrease DICAM toxicity have also been investigated.

Designed Polyhydroxyproline Helical Peptide with Ultrarobust Antifouling Capability for Electrochemical Sensing in Diverse Complex Biological Fluids.

Developing a generalized strategy for the nonfouling detection of biomarkers in diverse biological fluids presents a significant challenge. Herein, a polyhydroxyproline helical peptide (PHHP) was designed and adopted to fabricate electrochemical microsensors capable of detecting targets in various biological media. The PHHP possessed unique properties such as strong hydrophilicity, rigid structure, and lack of ionizable side-chain groups. Compared with common zwitterionic peptides (ZIPs), the PHHP exhibited similar antifouling capability but exceptional stability, allowing its antifouling performance to be unaffected by environmental alteration. The PHHP can prevent biofouling even in fluctuating pH conditions, high ionic strength environments, and the presence of high-valence ions and resist the protease hydrolysis. The PHHP-modified carbon fiber microelectrode was further immobilized with an aptamer to construct an antifouling microsensor for cortisol detection across diverse biofluids, and the microsensor exhibited acceptable accuracy and higher sensitivity than the ELISA method. In addition, different biological samples of mice were collected in situ using a microsensing device, and cortisol levels were analyzed in each specifically tailored region. This nonfouling sensing strategy based on PHHP allows a comprehensive assessment of biomarkers in both spatial and temporal dimensions in diverse biological environments, holding promising potential for early disease diagnosis and real-time health monitoring.

Engineering an antifouling electrochemical aptasensor based on a designed zwitterionic peptide for tetracycline detection in milk

Interference derived from nonspecific attachment of foulants (e.g. proteins) from food matrices (fouling) on sensor surfaces has always been a major issue in food safety sensing, deteriorating the stability and accuracy of detection. Engineering and introducing antifouling materials on sensors to strongly hydrate their surfaces is a promising approach to address this issue. Here, inspired by a bioactive peptide with antithrombotic function, a novel antifouling zwitterionic peptide (Z-peptide) with a sequence of NH2-CPPPPEKDQDK (C′−N') was designed. The antifouling performance of the proposed Z-peptides modified sensor surface was demonstrated in different protein solutions and milk samples (signal suppression rate as low as 1.87%). Molecular dynamics (MD) simulations reveal that a large number of hydrogen bonds and strong interaction forces are formed between Z-peptides and water molecules, contributing to the formation of a dense hydration layer on the sensor surface to resist nonspecific adsorption. An electrochemical aptasensor based on the Z-peptide was developed for tetracycline (TC) detection. The proposed sensor was able to detect TC with a wide linear range (0.01–100 ng mL−1) and a low limit of detection (LOD = 2.91 pg mL−1, S/N﹦3) and showed favorable specificity and stability. Given the excellent resistance to nonspecific adsorption, the antifouling sensor was capable of assaying TC in milk by diluting without other pretreatments (recoveries: 107.17%–110.16%).

A peptides-based biosensor with target-triggered charge-switchable property for simple and sensitive detection of Granzyme B

Granzyme B (GrB) is a serine protease released by natural killer cells and cytotoxic T lymphocytes during immune responses, which not only plays a role in tumor diagnosis but also provides valuable guidance during tumor treatment. In this work, we have designed a charge-switching peptide to fabricate an electrochemical biosensor for quantitative analysis of GrB. Specifically, the designed zwitterionic peptide is in an electrically neutral state before activation, and a door lock structure (proline) is constructed by utilizing the selectivity of carboxypeptidase A (CPA) to the carboxy-terminus of the peptide chain. The door lock is opened when the target is present, allowing CPA to hydrolyze the peptide. At this time, the peptide will convert from neutral to positive, triggering the assembly of a positively charged peptide layer on the electrode surface, resulting in a signal change. Studies have shown that the biosensor has good analytical performance, with a detection range of 0.01 pM–8 pM and a detection limit as low as 3.5 fM. Moreover, the developed biosensor has been effectively applied to the analysis of clinical samples, demonstrating its ability to monitor tumor progression and treatment with clinical applications.

Electrochemiluminescence bioassay with anti-fouling ability for determination of matrix metalloproteinase 9 secreted from living cells under external stimulation.

An electrochemiluminescence (ECL) bioassay with high sensitivity and anti-fouling ability was developed for determination of matrix metalloproteinase 9 (MMP-9) secreted from living cells under external stimulation. A peptide with sequence of CLGRMGLPGK and a new cyclometalated iridium(III) complex bearing carboxyl group, (pq)2Ir(dcbpy) (pq = 2-phenylquinoline, dcbpy = 2,2'-bipyridyl-4,4'-dicarboxyli acid, abbreviated as Ir) were employed as molecular recognition substrate and ECL emitter, respectively. The peptide was labelled with the Ir to form Ir-peptide as ECL probe. Ir-peptide was self-assembled onto Nafion and gold nanoparticles (AuNPs) modified glassy carbon electrode (AuNPs/Nafion/GCE) and then both of 6-mercapto-1-hexanol (MCH) and zwitterionic peptide as blocking reagents were co-assembled on Ir-peptide/AuNPs/Nafion/GCE to form an anti-fouling ECL peptide-based biosensor. MMP-9 can be quantified in the range 1.0-50ng·mL-1 with adetection limit of 0.50ng·mL-1 based on the decreased ECL intensity. Relative standard derivation was 2.3% for six fabricated anti-fouling ECL peptide-based biosensors after reaction with 50ng·mL-1 MMP-9. The anti-fouling ECL peptide-based biosensor can be used to monitor MMP-9 secreted from living cells under external stimulation. 96.0%-108.0% of recoveries were obtained in 60-diluted cell culture media. This study demonstrates that the ECL biosensor by the combination of iridium(III) complex-based sensitive ECL method and the anti-fouling interface provides a promising way for the determination of MMP-9 in biological sample, which is viable in clinical diagnosis and point-of-care test of protease.

Construction of Tumor Microenvironment‐Responsive Gene Carriers

AbstractPeptide‐ and polypeptide‐based self‐assembling gene delivery systems have received considerable attention owing to their inherent biocompatibility and bioactivity. Gene carriers based on elastin‐like polypeptides (ELPs) have been extensively studied because of their controllability and unique temperature responsiveness. The (EK)10‐PLGLAG‐Tat polypeptide sequence was selected for tumor gene delivery, with ELP serving as the hydrophobic core. In this sequence, a hydration layer can be formed on the surface of the carrier using the zwitterionic peptide segment (EK)10, which helps prevent the nonspecific adsorption of plasma proteins. Additionally, the MMP‐2 enzyme‐responsive PLGLAG peptide segment is responsible for exposing the cell‐penetrating peptide Tat specifically near tumor cells, facilitating the penetration of tumor cells. To introduce (EK)10‐PLGLAG‐Tat into the self‐assembling carrier while ensuring its bioactivity, a leucine zipper ZR/ZE with opposite charges was used to link it to the ELP. Because of its high specificity and low systemic toxicity, the carrier was named environmentally responsive gene carrier (ERGV). Experimental results demonstrated that the ERGV effectively removed (EK)10 in MMP‐2 overexpressed environments, altering the surface charge from negative to positive and facilitating ssDNA delivery into tumor cells. These findings highlight the potential of ERGVs as a safe and efficient method for targeted gene delivery to tumors.

Zwitterionic peptides: Tunable next-generation stealth nanoparticle modifications.

Adsorption of proteins to nanoparticles (NPs), a complex process that results in a protein corona, is controlled by NP surface properties that define NP interactions in vivo. Efforts to control adsorbed protein quantity through surface modification have led to improvements in circulation time or biodistribution. Still, current approaches have yet to be identified to control adsorbed protein identities within the corona. Here, we report the development and characterization of diverse zwitterionic peptides (ZIPs) for NP anti-fouling surface functionalization with specific and controllable affinity for protein adsorption profiles defined by ZIP sequence. Through serum exposure of ZIP-conjugated NPs and proteomics analysis of the resulting corona, we determined that protein adsorption profiles depend not on the exact composition of the ZIPs but on the sequence and order of charges along the sequence (charge motif). These findings pave the way for developing tunable ZIPs to orchestrate specific ZIP-NP protein adsorption profiles as a function of ZIP charge motif to better control cell and tissue specificity and pharmacokinetics and provide new tools for investigating relationships between protein corona and biological function. Furthermore, overall ZIP diversity enabled by the diversity of amino acids may ameliorate adaptive immune responses.

Phosphorylation of Oligopeptides: Design of Ultra-Hydrophilic Zwitterionic Peptides for Anti-Fouling Detection of Nucleic Acids in Saliva.

The construction of low-fouling biosensors for assaying biomarkers in complex biological samples remains a challenge, and the key limitation is the lack of effective anti-fouling materials. Inspired by the biomimetic process of protein phosphorylation, we herein designed a new phosphorylated peptide modified with the dihydrogen phosphate (-PO4H2) group, which significantly increased the hydrophilicity and anti-fouling capability of the peptide when compared with natural and normal peptides. Molecular simulation (MS) illustrated that, compared with the -COOH and -NH2 groups, the -PO4H2 group formed the most numbers of hydrogen bonds and stronger hydrogen bonds with water molecules. As a result, the PO4H2-oligopeptide was proved by MS to be able to attract the greatest number of water molecules, so as to form a compact layer of H2O to resist further adsorption of nonspecific biomolecules. The modification of electrodes with the designed PO4H2-oligopeptides, in addition to the adoption of neutral peptide nucleic acids (PNAs) as the sensing probes, ensured the fabrication of anti-fouling electrochemical biosensors capable of detecting nucleic acids in complex saliva. The constructed anti-fouling biosensor was able to detect the nucleic acid of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in undiluted saliva, with a wide linear response range (0.01 pM-0.01 μM) and a low limit of detection (LOD) of 3.4 fM (S/N = 3). The phosphorylation of oligopeptides offers an effective strategy to designing ultra-hydrophilic peptides suitable for the construction of promising anti-biofouling biosensors and bioelectronics.

Mussel-inspired proteins functionalize catheter with antifouling and antibacterial properties

Bacterial adhesion and subsequent biofilm formation on catheter can cause inevitably infection. The development of multifunctional antibacterial coating is a promising strategy to resist the bacteria adhesion and biofilm formation. Herein, a mussel-inspired chimeric protein MZAgP is prepared and employed to modify a variety of polymeric catheters. The MZAgP is composed of mussel-adhesive peptide, zwitterionic peptide, and silver-binding peptide, which can endow catheters with antifouling, bactericidal and biocompatibility performances. Expectedly, negligible biofilm is observed on the MZAgP coated catheters after incubating with bacteria for 120 h. And ignorable hemolysis and cytotoxicity are obtained on coated catheters. In addition, the modified catheters also display persistent antifouling and bacteriostatic properties throughout 168 h under hydrodynamic conditions. Moreover, the coated catheters can still remain excellent antifouling and antibacterial properties even after 2 months of storage. This multifunctional coating may be promising as antibacterial and antibiofilm biomaterial, and the coated catheters are potential in clinical application.

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.

A low-fouling electrochemical biosensor for biomarker detection in serum based on designed α/β-peptides with anti-enzymolysis and antifouling capabilities

The zwitterionic peptides, especially those composed of glutamic (E) and lysine (K) groups have drawn enormous attention as antifouling biomaterials owing to their strong hydration capability and biocompatibility. However, the susceptibility of α-amino acid K to the proteolytic enzymes in human serum limited the broad application of such peptides in biological media. Herein, a new multifunctional peptide with favorable stability in human serum was designed, and it was composed of three sections with immobilizing, recognizing and antifouling capabilities, respectively. The antifouling section was composed of alternating E and K amino acids, but the enzymolysis-susceptive amino acid α-K was replaced by the unnatural β-K. Compared with the conventional peptide composed of all α-amino acids, the α/β-peptide exhibited significantly enhanced stability and longer antifouling performance in human serum and blood. The electrochemical biosensor based on the α/β-peptide showed a favorable sensitivity to its target IgG, with a quite wide linear range from 100 pg mL−1 to 10 μg mL−1 and a low detection limit (33.7 pg mL−1, S/N = 3), and it was promising for the detection of IgG in complex human serum. The tactic of designing antifouling α/β-peptides offered an efficient way to develop low-fouling biosensors with robust operation in complex body fluids.

Prominent enhancement of peptide-mediated targeting efficiency for human hepatocellular carcinomas with composition-engineered protein corona on gold nanoparticles

We examined the feasibility of optimizing protein corona composition to improve the targeting efficiency of a tumor targeting peptide (Pep2) functionalized AuNPs (Au-Pep2) by coupling zwitterionic peptide (EK) and stearine (fat) separately or simultaneously. In vitro results demonstrated that Au-Pep2-EK and Au-Pep2-EK-fat exhibited higher binding affinity towards tumor cells than Au-Pep2 in fetal bovine serum (FBS)- and mouse serum (MS)-containing medium. Such enhancement could be considered as a result of the anti-fouling peptide EK that can create a hydration layer to resist nonspecific protein adsorption, as well as fat modification for specific albumin binding. In vivo results further revealed that, at 24 h post i.v. injection, such engineering optimal Au-Pep2-EK-fat achieved nearly 10-fold and 2-fold greater tumor accumulation than Au-Pep2 and Au-Pep2-EK, respectively, which may attributed to the prolonged blood clearance half-life as a result of pre-albumin coating. This work suggests nanoparticle surface chemistry as a readily tunable parameter in future rational exploiting of protein corona, and provides a feasible strategy for improving the targeting efficiency of ligand-modified nanoparticles.