Nonspecific Protein Adsorption Research Articles

Fabrication of dextran-grafted magnetic polymer microspheres with low nonspecific protein adsorption as carriers for chemiluminescence immunoassays

Inhibiting the nonspecific protein adsorption on the surface of magnetic microspheres has become a pressing challenge for immunoassays. In this paper, a novel dextran-modified sandwich-type magnetic polymer microsphere was developed and demonstrated to be a promising carrier for chemiluminescence immunoassay (CLIA). Dextran-modified sandwich-type magnetic polymer microspheres (PFS-PGDN) were synthesized by surface-initiated atom transfer radical polymerization (SI-ATRP) and ring-opening reaction of epoxy and aminodextran on the surface of magnetic P(GMA-MMA)-NH2@Fe3O4@SiO2 (PFS) microspheres. Then, carboxylated dextran-modified sandwich-type magnetic polymer microspheres (PFS-PGDC) were prepared by the surface carboxylation of the microspheres, which allowed the prepared microspheres to better couple with nucleic acids or antibodies. It is found that after grafting dextran, magnetic PFS-PGDC microspheres could significantly reduce the nonspecific protein adsorption by over 90 %. The chemiluminescence immunoassay assay showed a reduction of the background value to a very low level, indicating that the magnetic spheres showed significant advantages in improving the sensitivity of the chemiluminescence assay. Moreover, the chemiluminescence sensitivity and signal values of the synthesized magnetic microspheres have reached high levels. Therefore, the magnetic microspheres synthesized here hold great promise for applications in the field of CLIA.

Fast-polymerized lubricant and antibacterial hydrogel coatings for medical catheters

Medical catheters are highly susceptible to friction and infection when intervening or implanting in the body, and to thrombosis when in contact with blood. Coating medical catheters with lubricant and antibacterial hydrogel is an effective strategy but struggle to achieve. Here, hydrogel coating on the catheter surface with lubrication and antibacterial properties was constructed by the rapid polymerization of acrylamide (AAM) and sulfobetaine methacrylate (SBMA) in the presence of quaternary ammonium chitosan (QCS) based on the redox-based cross-linking method. First, the medical catheter surface was decorated with a polyethyleneimine (PEI) adhesive layer. The pre-gel solution was then applied to the catheter surface, followed by immersion in an aqueous FeSO4·7H2O solution, where a large amount of SO4-• was generated by a redox reaction between ammonium persulfate (APS) and Fe2+, which rapidly triggered the monomer to cross-link to form the coating. Polyelectrolyte PEI as the adhesive layer could bind the coating to the substrate through hydrogen bonding interactions and confer antimicrobial properties to the coating with the assistance of QCS (antibacterial rate of 95.88 % against E. coli and 97.11 % against B. subtilis). The hydrogel coatings exhibited outstanding lubricity with a low coefficient of friction (COF ≈ 0.053) and excellent antifouling properties (resists non-specific protein adsorption, inhibits platelet adhesion and prevents thrombosis (The clotting time was extended from 25.6 s to 74.7 s)) based on the integration of SBMA. This work shed new light on the design of hydrogel coatings to achieve modification of the substrate surface.

Probing Protein Corona Formation around Gold Nanoparticles: Effects of Surface Coating.

There has been much interest in integrating various inorganic nanoparticles (nanoscale colloids) in biology and medicine. However, buildup of a protein corona around the nanoparticles in biological media, driven by nonspecific interactions, remains a major hurdle for the translation of nanomedicine into clinical applications. In this study, we investigate the interactions between gold nanoparticles and serum proteins using a series of dihydrolipoic acid (DHLA)-based ligands. We employed gel electrophoresis combined with UV-vis absorption and dynamic light scattering to correlate protein adsorption with the nature and size of the ligand used. For instance, we found that AuNPs capped with DHLA alone promote nonspecific protein adsorption. In comparison, capping AuNPs with polyethylene glycol- or zwitterion-appended DHLA essentially prevents corona formation, regardless of ligand charge and size. Our results highlight the crucial role of surface chemistry and core material in protein corona formation and offer valuable information for the design of colloidal nanomaterials for biological applications.

Functional surface modifications impact on the in vitro/in vivo toxicity and intracellular internalization behavior of mesoporous silica nanoparticles

The surface properties of nanocarriers, including morphology, charge and surface modification are closely associated with their in vivo toxicity, biodistribution and bioavailability, which further affect the therapeutic effect. Herein, a series of in vitro and in vivo studies, including hemolysis, protein adsorption, cytotoxicity, cellular uptake and in vivo acute toxicity were performed to investigate the influences of surface properties on the biocompatibility and intracellular internalization behavior of functionalized degradable dendritic mesoporous silica nanoparticles (DDMSNs). The results illustrated that hyaluronic acid-modified DDMSNs (DDMSNs-NH2-HA) nanocarriers showed lower hemolysis, non-specific protein adsorption and in vitro cytotoxicity compared to DDMSNs and aminated DDMSNs (DDMSNs-NH2). The HA-mediated efficient intracellular internalization and significant accumulation of DDMSNs-NH2-HA in A549 cells was observed by cellular uptake assays. Furthermore, compared to DDMSNs and DDMSNs-NH2 groups, no significant pathological abnormalities were found in the hematoxylin and eosin-stained sections of key organs induced by DDMSNs-NH2-HA nanocarriers for in vivo toxicity, indicating that the improvement of nanocarriers’ biocompatibility arose from HA modification. This work explored the influencing mechanism of surface properties on biological toxicity and intracellular internalization behavior of nanocarriers in vitro and in vivo, which provided an insight into the design of biocompatible nano-DDS by rational surface modifications.

Diblock Copolymers of Methacryloyloxyethyl Phosphorylcholine and Dopamine Methacrylamide: Synthesis and Real-Time Adsorption Dynamics by SEIRAS and RAIRS.

Amphiphilic diblock copolymers containing a block of 2-methacryloyloxyethyl phosphorylcholine (MPC) with unique properties to prevent nonspecific protein adsorption and enhance lubrication in aqueous media and a block of dopamine methacrylamide (DOPMA) distinguished by excellent adhesion performance were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization for the first time. The DOPMA monomer with an acetonide-protected catechol group (acetonide-protected dopamine methacrylamide (ADOPMA)) was used, allowing the prevention of undesirable side reactions during polymerization and oxidation during storage. The adsorption behavior of the diblock copolymers with protected and unprotected catechol groups on gold surfaces was probed using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy, surface-enhanced infrared absorption spectroscopy (SEIRAS), and reflection-absorption infrared spectroscopy (RAIRS). The copolymers pMPC-b-pADOPMA demonstrated physisorption with rapid adsorption and ultrasound-assisted desorption, while the copolymers pMPC-b-DOPMA exhibited chemical adsorption with slower dynamics but a stronger interaction with the gold surface. SEIRAS and RAIRS allowed proving the reorientation of the diblock copolymers during adsorption, demonstrating the exposure of the pMPC block toward the aqueous phase.

Durable plasma-mediated zwitterionic grafting on polymeric surfaces for implantable medical devices

Adverse body reactions to blood-contacting medical devices endanger patient safety and impair device functionality, with events invariably linked to nonspecific protein adsorption due to suboptimal material biocompatibility. To improve the safety and durability of such devices, herein we propose a strategy for introducing stable zwitterionic grafts onto polymeric surfaces via plasma functionalization. The resulting zwitterion-grafted substrates exhibit long-lasting superhydrophilicity, enabling antifouling and anti-thrombogenic properties. We demonstrate the successful modification of the surface elemental composition, morphology, and hydrophilicity, while retaining the underlying mechanical properties of the polymeric substrate. Furthermore, we optimise the fabrication process to ensure long-lasting modifications at least three months after fabrication. This strategy decreases fibrinogen adsorption by approximately 9-fold, and thrombosis by almost 75% when applied to a commercial polyurethane. Moreover, this process is universally applicable to a wide range of polymeric materials, even those with stable chemistry such as polytetrafluoroethylene.

Constructing a Hydrophilic Microsensor for High-Antifouling Neurotransmitter Dopamine Sensing.

Real-time sensing of dopamine is essential for understanding its physiological function and clarifying the pathophysiological mechanism of diseases caused by impaired dopamine systems. However, severe fouling from nonspecific protein adsorption, for a long time, limited conventional neural recording electrodes concerning recording stability. This study reported a high-antifouling nanocrystalline boron-doped diamond microsensor grown on a carbon fiber substrate. The antifouling properties of this diamond sensor were strongly related to the grain size (i.e., nanocrystalline and microcrystalline) and surface terminations (i.e., oxygen and hydrogen terminals). Experimental observations and molecular dynamics calculations demonstrated that the oxygen-terminated nanocrystalline boron-doped diamond microsensor exhibited enhanced antifouling characteristics against protein adsorption, which was attributed to the formation of a strong hydration layer as a physical and energetic barrier that prevents protein adsorption on the surface. This finally allowed for in vivo monitoring of dopamine in rat brains upon potassium chloride stimulation, thus presenting a potential solution for the design of next-generation antifouling neural recording sensors. Experimental observations and molecular dynamics calculations demonstrated that the oxygen-terminated nanocrystalline boron-doped diamond (O-NCBDD) microsensor exhibited ultrahydrophilic properties with a contact angle of 4.9°, which was prone to forming a strong hydration layer as a physical and energetic barrier to withstand the adsorption of proteins. The proposed O-NCBDD microsensor exhibited a high detection sensitivity of 5.14 μA μM-1 cm-2 and a low detection limit of 25.7 nM. This finally allowed for in vivo monitoring of dopamine with an average concentration of 1.3 μM in rat brains upon 2 μL of potassium chloride stimulation, thus presenting a potential solution for the design of next-generation antifouling neural recording sensors.

In Situ Spatiotemporal SERS Profiling of Bacterial Quorum Sensing by Hierarchical Hydrophobic Plasmonic Arrays in Agar Medium.

A feedback inhibition effect of high autoinducer levels on metabolite secretion in Chromobacterium subtsugae (C. subtsugae) was evidenced by in situ spatiotemporal surface-enhanced Raman spectroscopy (SERS) profiling. The hierarchical hydrophobic plasmonic array in agar medium is structured by oil/water/oil (OL/W/OH) triphasic interfacial self-assembly. The hydrophobic layer acts as a "door curtain" to selectively permit adsorption of a quorum sensing (QS)-regulated fat-soluble metabolite, i.e., violacein (Vio), and significantly blocks nonspecific adsorption of water-soluble proteins, etc. The SERS profiling clearly evidences that the diffusion of N-hexanoyl-l-homoserine lactone (C6-HSL) in agar medium quickly triggers the initial synthesis of Vio in C. subtsugae CV026 but surprisingly inhibits the intrinsic synthesis of Vio in C. subtsugae ATCC31532. The latter negative response might be related to the VioS repressor of ATCC31532, which negatively controls violacein production without influencing the expression of the CviI/R QS system. Moreover, two sender-receiver systems are constructed by separately coculturing CV026 or ATCC31532 with Hafnia alvei H4 that secretes large amounts of C6-HSL. Expectedly, the cocultivation similarly triggers the initial synthesis of Vio in CV026 but seems to have a quite weak negative effect on the intrinsic synthesis in ATCC31532. In fact, the negative regulation in ATCC31532 might be affected by a diffusion-dependent concentration effect. The H4 growth and its secretion of C6-HSL are a slow and continuous process, thereby avoiding the gathering of local high concentrations. Overall, our study put forward an in situ SERS strategy as an alternative to traditional bioluminescent tools for highly sensitively analyzing the spatiotemporal communication and cooperation in live microbial colonies.

One-step prepared of e-Gelatin-CNTs nano-composite fiber modified carbon fiber microelectrode for continuous dopamine monitoring: Characterization, biocompatibility evaluation and in vivo experiment

Fabricating electrochemical sensor capable of stable sensing in complex organism's environment will undoubtedly underpin key in the development of implanted electrochemical sensor. However, nonspecific protein adsorption can greatly reduce sensing sensitivity of electrode due to the abundance of protein in vivo. Herein, we aim to fabricating a modified layer of good protein adsorption resistance. The nano-composite fibers from gelatin with good hydrophily and multiwall carbon nanotubes (CNTs) for constructing on the surface of carbon fiber microelectrode using one-step electrospinning technology (e-Gelatin-CNTs/CFME). A comprehensive discussing on the protein adsorption resistance of e-Gelatin-CNTs/CFME that are, through the use of SEM, AFM, water contact angle, UV–vis, cyclic voltammetry and I-T. The resulting electrochemical sensor revealed stable sensing sensitivity in protein solution, a slightly decrease (0.02nA/μM). Furthermore, the sensor was successfully used for the detection of DA in human blood. More remarkable, e-Gelatin-CNTs nano-composite fibers presented excellent biocompatibility, which could meet the biosafety as implantation materials in vivo. This work provided a platform for the development of implantable electrochemical sensor.

Enhanced Adsorption Stability and Biofunction Durability with Phosphonate-Grafted, PEGylated Copolymer on Hydroxyapatite Surface.

Nonfouling surfaces are crucial in applications such as biosensors, medical implants, marine coatings, and drug delivery vehicles. However, their long-term coating stability and robust surface binding strength in physiological media remain challenging. Herein, a phosphonate-grafted, PEGylated copolymer on the hydroxyapatite (HA) surface is proposed to significantly improve the adsorption stability and thus enhance the biofunction durability accordingly. The phosphoryl (-PO3) grafted branch is employed in the functional polymer to facilitate attaching to the HA substrate. In addition, the polymer integrates the nonfouling polymer brushes of poly(ethylene glycol) (PEG) with the cell-adhesive moiety of cyclic Arg-Gly-Asp-d-Phe-Cys peptides (cRGD). A systematic study on the as-synthesized PEGylated graft copolymer indicates a synergistic binding mechanism of the NH2 and PO3 groups to HA, achieving a high surface coverage with desirable adsorption stability. The cRGD/PEGylated copolymers of optimized grafting architecture are proven to effectively adsorb to HA surfaces as a self-assembled copolymer monolayer, showing stability with minimal desorption even in a complex, physiological medium and effectively preventing nonspecific protein adsorption as examined with X-ray photoelectron spectroscopy (XPS) and a quartz crystal microbalance with dissipation (QCM-D). Direct adhesion assays further confirm that the enhanced coating stability and biofunction durability of the phosphonate-grafted, cRGD-PEGylated copolymer can considerably promote osteoblast attachment on HA surfaces, meanwhile preventing microbial adhesion. This research has resulted in a solution of self-assembly polymer structure optimization that exhibits stable nonfouling characteristics.

Surface-segregating zwitterionic copolymers to control poly(dimethylsiloxane) surface chemistry.

The use of microfluidic devices in biomedicine is growing rapidly in applications such as organs-on-chip and separations. Polydimethylsiloxane (PDMS) is the most popular material for microfluidics due to its ability to replicate features down to the nanoscale, flexibility, gas permeability, and low cost. However, the inherent hydrophobicity of PDMS leads to the adsorption of macromolecules and small molecules on device surfaces. This curtails its use in "organs-on-chip" and other applications. Current technologies to improve PDMS surface hydrophilicity and fouling resistance involve added processing steps or do not create surfaces that remain hydrophilic for long periods. This work describes a novel, simple, fast, and scalable method for improving surface hydrophilicity and preventing the nonspecific adsorption of proteins and small molecules on PDMS through the use of a surface-segregating zwitterionic copolymer as an additive that is blended in during manufacture. These highly branched copolymers spontaneously segregate to surfaces and rearrange in contact with aqueous solutions to resist nonspecific adsorption. We report that mixing a minute amount (0.025 wt%) of the zwitterionic copolymer in PDMS considerably reduces hydrophobicity and nonspecific adsorption of proteins (albumin and lysozyme) and small molecules (vitamin B12 and reactive red). PDMS blended with these zwitterionic copolymers retains its mechanical and physical properties for at least six months. Moreover, this approach is fully compatible with existing PDMS device manufacture protocols without additional processing steps and thus provides a low-cost and user-friendly approach to fabricating reliable biomicrofluidics.

Distinguishing anti-PEG antibodies by specificity for the PEG terminus using nanoarchitectonics-based antibiofouling cello-oligosaccharide platforms.

The conjugation of poly(ethylene glycol) (PEG) to therapeutic proteins or nanoparticles is a widely used pharmaceutical strategy to improve their therapeutic efficacy. However, conjugation can make PEG immunogenic and induce the production of anti-PEG antibodies, which decreases both the therapeutic efficacy after repeated dosing and clinical safety. To address these concerns, it is essential to analyze the binding characteristics of anti-PEG antibodies to PEG. However, distinguishing anti-PEG antibodies is still a difficult task. Herein, we demonstrate the use of antibiofouling cello-oligosaccharide assemblies tethering one-terminal methoxy oligo(ethylene glycol) (OEG) ligands for distinguishing anti-PEG antibodies in a simple manner. The OEG ligand-tethering two-dimensional crystalline cello-oligosaccharide assemblies were stably dispersed in a buffer solution and had antibiofouling properties against nonspecific protein adsorption. These characteristics allowed enzyme-linked immunosorbent assays (ELISAs) to be simply performed by cycles of centrifugation/redispersion of aqueous dispersions of the assemblies. The simple assays revealed that the specific OEG ligand-tethering assemblies could distinguish anti-PEG antibodies to detect a specific antibody that preferentially binds to the methoxy terminus of the PEG chain with 3 repeating ethylene glycol units. Furthermore, quantitative detection of the antibodies was successfully performed with high sensitivity even in the presence of serum. The detectable and quantifiable range of antibody concentrations covered those required clinically. Our findings open a new avenue for analyzing the binding characteristics of anti-PEG antibodies in biological samples.

Using Mesoporous Silica-Based Dual Biomimetic Nano-Erythrocytes for an Improved Antitumor Effect.

The nano-delivery system with a dual biomimetic effect can penetrate deeper in tumor microenvironments (TMEs) and release sufficient antitumor drugs, which has attracted much attention. In this study, we synthesized erythrocyte-like mesoporous silica nanoparticles (EMSNs) as the core loaded with doxorubicin (DOX) and coated them with calcium phosphate (CaP) and erythrocyte membrane (EM) to obtain DOX/EsPMs. The transmission electron microscopy (TEM), fluorescent co-localization and protein bands of SDS-PAGE were used to confirm the complete fabrication of EsPMs. The EsPMs with erythrocyte-like shape exhibited superior penetration ability in in vitro diffusion and tumor-sphere penetration experiments. Intracellular Ca2+ and ROS detection experiments showed that the CaP membranes of EsPMs with pH-sensitivity could provide Ca2+ continuously to induce reactive oxide species' (ROS) generation in the TME. The EM as a perfect "camouflaged clothing" which could confuse macrophagocytes into prolonging blood circulation. Hemolysis and non-specific protein adsorption tests proved the desirable biocompatibility of EsPMs. An in vivo pharmacodynamics evaluation showed that the DOX/EsPMs group had a satisfactory tumor-inhibition effect. These advantages of the nano-erythrocytes suggest that by modifying the existing materials to construct a nano-delivery system, nanoparticles will achieve a biomimetic effect from both their structure and function with a facilitated and sufficient drug release profile, which is of great significance for antitumor therapy.

Silica-coated magnetic nanorods with zwitterionic surface functionalization to overcome non-specific protein adsorption

Anisotropic magnetic nanoparticles are receiving growing interest for biomedical applications due to their interesting properties, particularly for MRI and magnetic hyperthermia. In this work, a two-step, relatively simple synthesis pathway of magnetite nanorods was optimised. A ligand from the catechol family, known for its high iron oxide surface affinity, was used to transfer them into aqueous phase. The magnetite nanorods were then coated with a layer of fluorescent silica, whose surface was functionalised in two ways: either by short poly(ethylene glycol) (PEG) chains or by sulfobetaine zwitterionic molecules. A wide range of techniques were used to thoroughly characterise their physical structure, magnetic properties and dispersion characteristics. Finally, a study of the adsorption of a fluorescent model protein revealed that zwitterionic sulfobetaine molecules were more effective than PEG chains in limiting the non-specific adsorption of this protein.

Biomimetic affinity membrane roll column for rapid purification of C-reactive protein

To in-depth explore the action mechanism of C-reactive protein (CRP) and precisely study its signaling pathways, it is essential to acquire high-purity CRP while preserving its intact structure and functionality. In this study, we propose and fabricate a high-density 2-methacryloyloxyethyl phosphorylcholine (MPC)-modified membrane roll column (MPC-MRC) using a surface-initiated atom transfer radical polymerization (SI-ATRP) approach, which can overcome these limitations (long incubation time and low adsorption capacity) of conventional enrichment materials. The MPC-MRC incorporates a high-density 2-hydroxyethyl methacrylate polymer brush to prevent non-specific protein adsorption and multiple MPC polymer brush layers for high-performance enrichment of CRP in the company of calcium ions. Furthermore, the MPC-MRC exhibits high permeability, hydrophilicity, and mechanical strength. Compared to previous technologies, this novel material demonstrates significantly higher CRP binding capacity (310.3 mg/g), shorter processing time (only 15 min), and lower cost (only 12 USD/column). Notably, the MPC-MRC enables fast and effective purification of CRP from both human and rat serum, exhibiting good selectivity, recovery (> 91.3 %), and purity (> 95.2 %). Thus, this proposed purification approach based on MPC-MRC holds great potential for target protein enrichment from complex samples, as well as facilitating in-depth studies of its biological functions.

Inhibition of non-specific protein adsorption on PMMA surface: The role of surface modification

Mitigating non-specific adsorption (NSA) occurring on the surface of microfluidic devices plays a critical role in the detection of early protein biomarkers for clinical diagnosis. Surface-modified methods commonly used in the formation of microfluidic channels include BSA coating, PEG grafting, and Plasma cleaning. The surface composition and microstructure of PMMA surfaces were characterized by Fourier transfer infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), water contact angles (CA), and atomic force microscopy (AFM) measurements. The NSA on surfaces of bovine serum albumin (BSA) labeled with fluorescein isothiocyanate (FITC) were investigated by microfluidics and fluorescence microscopy. The results showed that the hydrophobicity of the PMMA surface was enhanced after modification with PEG. We further evaluated their anti-protein adsorption properties under a mild alkaline (PH 7.4) condition, including concentration, reaction time, and sample volume. The BSA coating had the best anti-protein adsorption effect, reaching over 87.6%. The anti-protein adsorption effect of the plasma cleaning method is slightly inferior to that of BSA coating, at 86.1%, but the modification process is simpler and faster. Due to the insufficient stability of PEG, its resistance to protein adsorption decreases as the concentration increases.

Aligned skeletal muscle assembly on a biofunctionalized plant leaf scaffold.

Decellularized plant scaffolds have drawn attention as alternative tissue culture platforms due to their wide accessibility, biocompatibility, and diversity of innate microstructures. Particularly, in this work, monocot leaves with innate uniaxial micropatterned topography were utilized to promote cell alignment and elongation. The leaf scaffold was biofunctionalized with poly(PEGMEMA-r-VDM-r-GMA) copolymer that prevented non-specific protein adsorption and was modified with cell adhesive RGD peptide to enable cell adhesion and growth in serum-free media. The biofunctionalized leaf supported the adhesion, growth, and alignment of various human cells including embryonic stem cells (hESC) derived muscle cells. The hESC-derived myogenic progenitor cells cultured on the biofunctionalized leaf scaffold adopted a parallel orientation and were elongated along the leaf topography. These cells showed significant early myogenic differentiation and muscle-like bundled myotube formation. The aligned cells formed compact myotube assemblies and showed uniaxial muscle contraction under chemical stimulation, a critical requirement for developing functional skeletal muscle tissue. Polymer-functionalized plant leaf scaffolds offer a novel human cell culture platform and have potential in human tissue engineering applications that require parallel alignment of cells. STATEMENT OF SIGNIFICANCE: Plant scaffolds are plentiful sources in nature and present a prefabricated construct to present topographical cues to cells. Their feature width is ideal for human cell alignment and elongation, especially for muscle cells. However, plant scaffolds lack proteins that support mammalian cell culture. We have developed a polymer coated leaf scaffold that enables cell adhesion and growth in serum-free media. Human muscle cells cultured on the biofunctionalized leaf, aligned along the natural parallel micro-patterned leaf topography, and formed muscle-like bundled myotube assemblies. These assemblies showed uniaxial muscular contraction, a critical requirement for developing functional skeletal muscle tissue. The biodiversity of the plant materials offers a novel human cell culture platform with potential in human tissue engineering.

Ultrasensitive Ratiometric Electrochemiluminescence Sensor with an Efficient Antifouling and Antibacterial Interface of PSBMA@SiO2-MXene for Oxytetracycline Trace Detection in the Marine Environment.

The sensitivity and accuracy of electrochemiluminescence (ECL) sensors for detecting small-molecule pollutants in environmental water are affected not only by nonspecific adsorption of proteins and other molecules but also by bacterial interference. Therefore, there is an urgent need to develop an ECL sensor with antifouling and antibacterial functions for water environment monitoring. Herein, a highly efficient antifouling sensing interface (PSBMA@SiO2-MXene) based on zwitterionic sulfobetaine methacrylate (SBMA) antifouling nanospheres (NPs) and two-dimensional MXene nanosheets was designed for the sensitive detection of oxytetracycline (OTC), an antibiotic small-molecule pollutant. Specifically, SBMA with good hydrophilicity and electrical neutrality was connected to SiO2 NPs, thus effectively reducing protein and bacterial adsorption and improving stability. Second, MXene with a high specific surface area was selected as the carrier to load more antifouling NPs, which greatly improves the antifouling performance. Meanwhile, the introduction of MXene also enhances the conductivity of the antifouling interface. In addition, a ratio-based sensing strategy was designed to further improve the detection accuracy and sensitivity of the sensor by utilizing Au@luminol as an internal standard factor. Based on antifouling and antibacterial interfaces, as well as internal standard and ratiometric sensing strategies, the detection range of the proposed sensor was 0.1 ng/mL to 100 μg/mL, with a detection limit of 0.023 ng/mL, achieving trace dynamic monitoring of antibiotics in complex aqueous media.

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.

Sulfur dioxide-releasing polymeric micelles based on modified hyaluronic acid for combined cancer therapy

In this study, an amphiphilic polymer mPEG-HA(SA)-DNs was designed and synthesized to fabricate a multifunctional micellar system to enhance the therapeutic efficacy and reduce the toxic effect of paclitaxel (PTX). The polymer was prepared by introducing mPEG, stearic acid (SA) and 2,4-dinitrobenzenesulfonic acid (DNs) to the backbone of hyaluronic acid (HA). With above modifications, the fabricated micelles could encapsulate PTX in the core with high drug loading. The optimized PTX-loaded micelles had a mean size of 158.3 nm. Upon the effect of mPEG, the mPEG-HA(SA)-DNs micelles reduced the non-specific protein adsorption. In vitro drug release study revealed the excellent glutathione (GSH)-triggered PTX release behavior of the micelles. Moreover, GSH could trigger the detachment of DNs segment from mPEG-HA(SA)-DNs, and result in the release of SO2. In vitro and in vivo antitumor efficacy studies demonstrated that the PTX-loaded mPEG-HA(SA)-DNs micelles exhibited outstanding tumor suppression effect. The micelles would be potential carriers for combination cancer therapy by SO2 and PTX.