27 research outputs found

    Designs of Zwitterionic Interfaces and Membranes

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    Zwitterionic materials are the latest generation of materials for nonfouling interfaces and membranes. They outperform poly­(ethylene glycol) derivatives because they form tighter bonds with water molecules and can trap more water molecules. This feature article summarizes our laboratory’s fundamental developments related to the functionalization of interfaces and membranes using zwitterionic materials. Our molecular designs of zwitterionic polymers and copolymers, sulfobetaine-based, carboxybetaine-based, or phosphobetaine-based, are first reviewed. Then, the strategies used to functionalize surfaces/membranes by coating, grafting onto, grafting from, or in situ modification are examined and discussed, and the third part of this article shifts the focus to key applications of zwitterionic materials. Finally, some potential future directions for molecular designs, functionalization processes, and applications are presented

    Zwitterionic Polyhydroxybutyrate Electrospun Fibrous Membranes with a Compromise of Bioinert Control and Tissue-Cell Growth

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    We present a method for surface modification by thermal-evaporation self-assembling of poly­(3-hydroxybutyrate) (PHB) fibrous membranes with a copolymer of hydrophobic octadecyl acrylate repeat units and hydrophilic zwitterionic 4-vinylpyridine blocks, zP­(4VP-<i>r</i>-ODA), in view of controlling biofoulant–fiber interactions. PHB is of interest as a material for bioscaffolding, but its disadvantage is its hydrophobicity, which leads to unwanted interactions with proteins, blood cells, or bacteria. Surface modification of electrospun PHB fibers addresses this issue because the hydrophilicity of the membranes is improved, leading to a significant reduction in bovine serum albumin (92%), lysozyme (73%), and fibrinogen (50%) adsorption. From a coating density of 0.78 mg/cm<sup>2</sup>, no bacteria interacted with the fibers, and from 1.13 mg/cm<sup>2</sup>, excellent hemocompatibility of membranes was measured from thrombocytes, erythrocytes, leukocytes, and whole blood attachment tests. Additionally, HT-1080 fibroblasts were observed to develop in contact with the fibers after 3–7 days of incubation (cell density up to 329 ± 16 cells/mm<sup>2</sup>), suggesting that zP­(4VP-<i>r</i>-ODA) provides an adequate humid environment for their growth. Providing an effective control of the surface chemistry and of the coating density, the association of PHB and zP­(4VP-<i>r</i>-ODA) can promote the growth of fibroblasts, still maintaining resistance to unwanted biofoulants, and appears to be a promising composite material for tissue engineering

    Counterion-Activated Nanoactuator: Reversibly Switchable Killing/Releasing Bacteria on Polycation Brushes

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    A strategy to release attached bacteria from surface-grafted bactericidal poly­((trimethylamino)­ethyl methacrylate chloride) (pTMAEMA) brushes has been proposed. The pTMAEMA brushes were fabricated via the surface-initiated atom transfer radical polymerization for contact killing of bacteria, including Escherichia coli, Staphylococcus epidermidis and Stenotrophomonas maltophilia. The bacteria-conditioning surfaces, afterward, were washed with electrolyte solutions containing anions with different lipophilic characteristic, charge density, polarity and adsorbility to quaternary ammonium groups in polymers. Because of the special ion-pairing interactions, the interfacial properties, including wettability and ζ-potential, can be manipulated in a controlled manner. Therefore, the counterion-assisted modulation of pTMAEMA brushes facilitates the bacterial release and regeneration of antimicrobial polymer films. The physicochemical properties of polymer brushes and their interactions with counterions were characterized using an ellipsometer, contact angle goniometer, X-ray photoelectron spectroscopy and an electrokinetic analyzer. The repetitive killing and releasing actions of pTMAEMA through unlocking and locking counterions were demonstrated, showing the robust effectiveness of the pTMAEMA-based nanoactuator in controlling the physical action by the chemical stimuli. The real-world implementation of the nanoactuator was demonstrated with a surgical scalpel by repelling killed bacteria and retaining reusability

    Reduced Blood Cell Adhesion on Polypropylene Substrates through a Simple Surface Zwitterionization

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    To overcome the thrombogenic reactions of hydrocarbon-based biomaterials in clinical blood treatment, we introduce a model study of surface zwitterionization of a polypropylene (PP) substrate using a set of well-defined copolymers for controlling the adhesion of blood cells in vitro. Random and block copolymers containing zwitterionic units of 2-methacryloyloxyethyl phosphorylcholine (MPC), [3-(methacryloylamino)­propyl]­dimethyl­(3-sulfopropyl)­ammonium hydroxide inner salt (SBAA), or nonionic units of 2-hydroxyethyl methacrylate (HEMA) with a controlled hydrophobic segment of 70% <i>n</i>-butyl methacrylate (BMA) units in these polymers were synthesized through reversible addition–fragmentation chain transfer polymerization. A systematic study of how zwitterionic and nonionic copolymer architectures associated with controlled chain orientation via hydration processes affect blood compatibility is reported. The surface wettability of PP substrates coated with the block copolymer with poly­(MPC) (PMPC) segments was higher than that of the random copolymer poly­(MPC-random-BMA). However, only the random copolymers with SBAA units demonstrate a higher surface wettability. The PP substrate coated with nonionic copolymers containing HEMA units showed relatively lower hydration capability associated with higher protein adsorption, platelet adhesion, and leukocyte attachment than those with zwitterionic copolymers. The random copolymer poly­(SBAA-random-BMA) coated on the PP substrates exhibited resistance to cell adhesion in human whole blood at a level comparable to that of MPC copolymers. An ideal zwitterionic PP substrate could be obtained by coating it with a block copolymer composed of PMPC and poly­(BMA) (PBMA) segments, PMPC-<i>block</i>-PBMA. The water contact angle decreased dramatically from approximately 100° on the original PP substrate to 11° within 30 s. The number of blood cells attached on PMPC-<i>block</i>-PBMA decreased significantly to less than 2.5% of that on original PP. These results prove that the rational design of zwitterionic polymers incorporated with a hydrophobic anchoring portion provides a promising approach to reduce blood cell adhesion and protein adsorption of hydrocarbon-based biomaterials applied in direct contact with human whole blood

    RNA Origami Functions as a Self-Adjuvanted Nanovaccine Platform for Cancer Immunotherapy

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    Peptide-based vaccines have been widely investigated in cancer immunotherapy. Despite their high specificity, safety, and low production cost, these vaccines have shown limited success in clinical studies, owing to their poor immunogenicity. Extensive efforts have been devoted to increasing the immunogenicity of peptide vaccines by mixing peptides with adjuvants and/or promoting their delivery to tumor-draining lymph nodes (TdLNs) for better antigen presentation by and maturation of dendritic cells. Among these efforts, the exploration of various nanoparticles has been at the forefront of the rational design and construction of peptide-based vaccines. Here, we present a nanovaccine platform that is built on a self-assembled RNA origami (RNA-OG) nanostructure. As previously reported, this RNA-OG nanostructure is a potent toll-like receptor (TLR)­3 agonist. In addition, due to its robust synthesis and versatility in modification, RNA-OG could be readily linked to peptides of interest. Thus, these RNA-OG nanostructures function as adjuvanted nanocarriers to construct RNA-OG-peptide nanovaccines that are uniform in size, consistent in peptide loading, and highly stable. Here, we demonstrate that the assembled RNA-OG-peptide nanovaccines induced dendritic cell maturation, reduced tumor-mediated immunosuppression, and mobilized tumor-specific CD8+ T cell responses at the tumor site. Together, these actions led to the elicitation of an effective antitumor immunity that increased the survival of tumor-bearing mice. The combination of RNA-OG-based nanovaccines with the α-PD-1 immune checkpoint blockade further enhanced the immunity. Hence, our RNA-OG nanostructures represent a robust, simple, and highly effective platform to empower peptide-based vaccines for cancer immunotherapy

    Applying Thermosettable Zwitterionic Copolymers as General Fouling-Resistant and Thermal-Tolerant Biomaterial Interfaces

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    We introduced a thermosettable zwitterionic copolymer to design a high temperature tolerance biomaterial as a general antifouling polymer interface. The original synthetic fouling-resistant copolymer, poly­(vinylpyrrolidone)-<i>co</i>-poly­(sulfobetaine methacrylate) (poly­(VP-<i>co</i>-SBMA)), is both thermal-tolerant and fouling-resistant, and the antifouling stability of copolymer coated interfaces can be effectively controlled by regulating the VP/SBMA composition ratio. We studied poly­(VP-<i>co</i>-SBMA) copolymer gels and networks with a focus on their general resistance to protein, cell, and bacterial bioadhesion, as influenced by the thermosetting process. Interestingly, we found that the shape of the poly­(VP-<i>co</i>-SBMA) copolymer material can be set at a high annealing temperature of 200 °C while maintaining good antifouling properties. However, while the zwitterionic PSBMA polymer gels were bioinert as expected, control of the fouling resistance of the PSBMA polymer networks was lost in the high temperature annealing process. A poly­(VP-<i>co</i>-SBMA) copolymer network composed of PSBMA segments at 32 mol % showed reduced fibrinogen adsorption, tissue cell adhesion, and bacterial attachment, but a relatively higher PSBMA content of 61 mol % was required to optimize resistance to platelet adhesion and erythrocyte attachment to confer hemocompatibility to human blood. We suggest that poly­(VP-<i>co</i>-SBMA) copolymers capable of retaining stable fouling resistance after high temperature shaping have a potential application as thermosettable materials in a bioinert interface for medical devices, such as the thermosettable coating on a stainless steel blood-compatible metal stent investigated in this study

    Expression duration of <i>in vivo</i> transfected plasmid DNA.

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    <p>DNA (10 µg) was gently mixed with PEI at an N/P ratios of 0.5 or PDMAEMA at weight ratios of 0.25, 0.5 and 1. DNA/PEI and PDMAEMA complexes were then injected into the thigh muscle of mice and transfected by sonoporation. Luciferase activity in Balb/C mice was measured by an IVIS system on gene transfection with (right leg) or without (left leg) US exposure. (A) Quantification of the signal produced in mice muscle after transfection of each formulation (B) without and (C) with US exposure. All results are expressed as the mean ± SEM for five independent measurements (n = 5). <i>*P</i><0.05 vs. PDMAEAM 1.</p

    Probing the Structural Dependence of Carbon Space Lengths of Poly(<i>N</i>‑hydroxyalkyl acrylamide)-Based Brushes on Antifouling Performance

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    Numerous biocompatible antifouling polymers have been developed for a wide variety of fundamental and practical applications in drug delivery, biosensors, marine coatings, and many other areas. Several antifouling mechanisms have been proposed, but the exact relationship among molecular structure, surface hydration property, and antifouling performance of antifouling polymers still remains elusive. Here this work strives to provide a better understanding of the structure–property relationship of poly­(<i>N</i>-hydroxyalkyl acrylamide)-based materials. We have designed, synthesized, and characterized a series of polyHAAA brushes of various carbon spacer lengths (CSLs), that is, poly­(<i>N</i>-hydroxymethyl acrylamide) (polyHMAA), poly­(<i>N</i>-(2-hydroxyethyl)­acrylamide) (polyHEAA), poly­(<i>N</i>-(3-hydroxypropyl)­acrylamide) (polyHPAA), and poly­(<i>N</i>-(5-hydroxypentyl)­acrylamide) (polyHPenAA), to study the structural dependence of CSLs on their antifouling performance. HMAA, HEAA, HPAA, and HPenAA monomers contained one, two, three, and five methylene groups between hydroxyl and amide groups, while the other groups in polymer backbones were the same as each other. The relation of such small structural differences of polymer brushes to their surface hydration and antifouling performance was studied by combined experimental and computational methods including surface plasmon resonance sensors, sum frequency generation (SFG) vibrational spectroscopy, cell adhesion assay, and molecular simulations. Antifouling results showed that all polyHAAA-based brushes were highly surface resistant to protein adsorption from single protein solutions, undiluted blood serum and plasma, as well as cell adhesion up to 7 days. In particular, polyHMAA and polyHEAA with the shorter CSLs exhibited higher surface hydration and better antifouling ability than polyHPMA and polyHPenAA. SFG and molecular simulations further revealed that the variation of CSLs changed the ratio of hydrophobicity/hydrophilicity of polymers, resulting in different hydration characteristics. Among them, polyHMAA and polyHEAA with the shorter CSLs showed the highest potency for surface hydration and antifouling abilities, while polyHPenAA showed the lowest potency. The combination of both hydroxyl and amide groups in the same polymer chain provides a promising structural motif for the design of new effective antifouling materials

    Effect of PEI and PDMAEMA on intracellular uptake of DNA monitored by flow cytometry 24 h following exposures.

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    <p>Fluorescence labeled DNA was mixed with PEI or PDMAEMA in culture cell plates before being treated with US. (B) The overall fluorescence intensities of cultured cells and (C) the percentage of cells with fluorescence are also shown. All results are expressed as the mean ± SEM for four independent measurements. *<i>P</i><0.05 vs. PEI group (regardless of US exposure).</p
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