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MACROMOLECULAR BIOSCIENCE · 2023 ·Vol. 23 ·期 4 ·2200554 · IF 4.6

Injectable Polyzwitterionic Lubricant for Complete Prevention of Cardiac Adhesion

Yi Wang,Weijie Zhai,Hongyu Zhang,Shujie Cheng,Jinghua Li

After cardiac surgery, tissue damage to the heart may cause adhesion between heart and its surrounding tissues. Post-operative cardiac adhesion may lead to limited normal cardiac function, decreased quality of cardiac surgery, and increased risk of major bleeding during reoperation. Therefore, it is necessary to develop an effective anti-adhesion therapy to overcome cardiac adhesion. An injectable polyzwitterionic lubricant is developed to prevent adhesion between the heart and surrounding tissues and to maintain normal pumping function of the heart. This lubricant is evaluated in a rat heart adhesion model. Poly (2-methacryloyloxyethyl phosphorylcholine) (i.e., PMPC) polymers are successfully prepared via free radical polymerization of monomer MPC, and the optimal lubricating performance, biocompatibility both in vitro and in vivo is demonstrated. Besides, a rat heart adhesion model is conducted to evaluate the bio-functionality of lubricated PMPC. The results prove that PMPC is a promising lubricant for complete adhesion-prevention. The injectable polyzwitterionic lubricant shows excellent lubricating properties and biocompatibility and can effectively prevent cardiac adhesion.

CAS / MDL: 7727-54-0
研究领域: 生物材料 · 心血管外科 · 组织工程 · 生物医学工程
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Science China-Chemistry · 2025 · IF 9.7

Lung-targeted polyzwitterionic lipid nanoparticles for effective treatment of lung inflammation

Zhang Wen,Li Jiaxin,Wang Nan,Li Muzi,Peng Chen,Zhang Xinyue,Ouyang Guanghui,Li Yan

Lipid nanoparticles (LNPs) are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease treatment. Although LNPs are particularly advantageous for in vivo delivery, the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly challenging. To address this issue, we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine) (PMPC) modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA (siRNA). Three libraries with 90 PMPC-LNPs@siRNA were established. The polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about 90%. The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin, mediating lung-targeted delivery of siRNA. With good cellular uptake and endo/lysosomal escape ability, in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α (TNF-α) could significantly down-regulate the TNF-α in mRNA and protein levels, and improved the pathological features of lung inflammation. Polyzwitterionic PMPC-LNPs@siRNA achieved safe and efficient treatment of lung inflammation. Therefore, this work offered a promising siRNA therapeutic approach for lung diseases.

CAS / MDL: 67881-98-5 7757-82-6
研究领域: 药学 · 纳米技术 · 分子生物学 · 治疗学
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Friction · 2022 ·Vol. 11 ·期 6 ·938-948 · IF 4.924

Synovial fluid-inspired biomimetic lubricating microspheres: Zwitterionic polyelectrolyte brushes-grafted microgels

Liu Guoqiang,Feng Yang,Gao Xiaohua,Chen Zhuo,Zhao Nan,Zhou Feng,Liu Weimin

Synovial fluid is made up of various biomacromolecules, including hyaluronic acid, aggrecans, lubricins, and phosphatidylcholine lipid, which are assembled onto the surface of articular cartilage in a gel state. Among them, brush-like biomacromolecules or assemblies have a vital effect on human joint lubrication. Inspired by this, the combination of brush-like molecular structures and gel-like assembly may be an efficient approach for the synthesis of biomimetic lubricating matters. Learning from the lubrication system of human joints, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brushes grafted poly(N-isopropylacrylamide-co-acrylic acid) (poly(NIPAAm-co-AA)) microgels, abbreviated as MBs-g-MGs, were synthesized as one kind of biomimetic lubricating additives. It is worth noting that this bionic strategy considered both molecular structure and assembled form, which enabled this hairy microgel to achieve low friction in aqueous medium. Meanwhile, the effective lubrication was still achieved when using MBs-g-MGs at high temperature, indicating that this microgel maintains a good lubricating effect over a wide range of temperature. In addition, this kind of microgel possessed good biocompatibility, which laid the foundation for potential biomedical applications. Looking beyond, these biomimetic microgels may provide an effective lubricating effect for water-based sliding interfaces, especially in biomedical systems.

研究领域: 材料科学 · 生物医学工程 · 摩擦学 · 聚合物化学
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Regenerative Biomaterials · 2024 · IF 5.6

Polyzwitterion-grafted decellularized bovine intercostal arteries as new substitutes of small-diameter arteries for vascular regeneration

Xia Yuan,Rao Zilong,Wu Simin,Huang Jiayao,Zhou Haiyun,Li Hanzhao,Zheng Hui,Guo Daxin,Quan Daping,Ou Jing-Song,Bai Ying,Liu Yunqi

Coronary artery bypass grafting is acknowledged as a major clinical approach for treatment of severe coronary artery atherosclerotic heart disease. This procedure typically requires autologous small-diameter vascular grafts. However, the limited availability of the donor vessels and associated trauma during tissue harvest underscore the necessity for artificial arterial alternatives. Herein, decellularized bovine intercostal arteries were successfully fabricated with lengths ranging from 15 to 30 centimeters, which also closely match the inner diameters of human coronary arteries. These decellularized arterial grafts exhibited great promise following poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) grafting from the inner surface. Such surface modification endowed the decellularized arteries with superior mechanical strength, enhanced anticoagulant properties, and improved biocompatibility, compared to the decellularized bovine intercostal arteries alone, or even those decellularized grafts modified with both heparin and vascular endothelial growth factor (VEGF). After replacement of the carotid arteries in rabbits, all surface-modified vascular grafts have shown good patency within 30 days post-implantation. Notably, strong signal was observed after α-SMA immunofluorescence staining on the PMPC-grafted vessels, indicating significant potential for regenerating the vascular smooth muscle layer and thereby restoring full structures of the artery. Consequently, the decellularized bovine intercostal arteries surface modified by PMPC can emerge as a potent candidate for small-diameter artificial blood vessels, and have shown great promise to serve as viable substitutes of arterial autografts.

CAS / MDL: 7631-90-5
研究领域: 生物材料 · 组织工程 · 血管外科 · 生物医学工程
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JOURNAL OF POLYMER SCIENCE · 2024 · IF 3.9

Introducing Antifouling Properties Onto Janus-Like Decellularized Corneas via Graft-From Zwitterionic Polymers

Simin Wu,Jiandong Han,Xiukai Guo,Zilong Rao,Kexin Zhang,Daping Quan,Ying Bai

The lack of endothelial layer hinders the use of decellularized corneal stroma in keratoplasty, resulting in adverse effects, such as non-specific protein adsorption and corneal oedema after implantation, which leads to rapid failure of the ophthalmic implants. In this study, superhydrophilic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was gently introduced to the porcine-derived decellularized corneal stroma matrix (pDCSM), aiming to resist undesirable biofilm adsorption within the ocular environment. After complete decellularization, the pDCSM was first methacrylated by the integration of methacrylic anhydride. Consecutively, PMPC was only grafted from the back surface (endothelium side) of the methacrylated pDCSM through surface-initiated free radical polymerization. This one-side surface-modified pDCSM not only retained good optical transmittance and mechanical properties that were comparable to the untreated pDCSM, but both surfaces of the same artificial cornea also showed non-cytotoxicity and good biocompatibility. Moreover, the PMPC-grafted back surface exhibited considerable antifouling properties that resisted both protein and cell adhesion. Consequently, such Janus-like artificial cornea holds great promise in future ophthalmic applications, which may serve as a springboard for the design of versatile decellularized extracellular matrix based biomedical implants with Janus-like properties. Graphical Surface initiated PMPC grafting on the back side of decellularized corneal stromal matrices resulted in Janus-like scaffolds for potential ophthalmic applications.

CAS / MDL: 9048-46-8 7727-54-0
研究领域: 生物材料 · 组织工程 · 眼科 · 聚合物化学 · 生物医学工程
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Polymer Chemistry · 2020 ·Vol. 11 ·期 13 ·2360-2369 · IF 5.342

Diselenide-crosslinked zwitterionic nanogels with dual redox-labile properties for controlled drug release

Yefei Tian,Miao Lei,Luke Yan,Feifei An

Drug delivery systems developed from zwitterionic polymers have intriguing antifouling properties. Combining these with stimuli-responsiveness, we fabricated a new type of zwitterionic nanogel with dual redox-labile properties by copolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and a diselenide bond-containing crosslinker through reflux precipitation polymerization. Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-based nanogels show high protein adsorption resistibility and colloidal stability at high salt concentrations. By incorporation of diselenide bonds into polymer networks, the nanogels are endowed with unique dual redox-labile properties that lead to their efficient degradation into short polymers either in a reducing environment (GSH) or in an oxidative environment (H2O2). Nanogels loaded with anticancer drugs (doxorubicin, DOX) display a finely controlled release behavior and low leakage of DOX under physiological conditions (15.0% in 24 h), but rapid and sufficient release under reducing conditions (88.3% in 24 h) or under oxidative conditions (82.2% in 24 h). Cell viability assays reveal that the blank nanogels have no cytotoxicity within a wide concentration range, while DOX-loaded nanogels present a significant inhibitive effect against tumor cells.

研究领域: 药学 · 纳米技术 · 材料科学 · 生物医学工程
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RSC Advances · 2017 ·Vol. 7 ·期 34 ·20766-20778 · IF 3.108

Construction of biomimetic long-circulation delivery platform encapsulated by zwitterionic polymers for enhanced penetration of blood–brain barrier

Nan Wang,Xin Jin,Xinyuan Zhu

The effective treatments for central nervous system (CNS) diseases are impeded mostly by the existence of the blood–brain barrier (BBB). The accumulation of therapeutic drugs inside the brain is far from the therapy threshold, which is closely related to the transient circulation time of drugs and their carriers. Herein, a core–shell protein-based long-circulation delivery platform was constructed. Through in situ free radical polymerization, a zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was modified on the surface to prolong the circulation lifetime with a biomimetic structure induced by a phosphorylcholine (PC) head-group similar to the lipids in the outer membrane of living cells. A cell-penetrating peptide, HIV-1 trans-activating transcriptor (TAT) was conjugated on the surface of the protein-based nanoparticles, endowing the delivery platform with BBB-crossing ability. The BBB-permeability of the nanoparticles was investigated both in vitro and in vivo. Encapsulated with zwitterionic polymer PMPC, the nanoparticles showed a long circulation lifetime due to strong resistance to nonspecific adsorption and provided a better chance for BBB penetration. The delivery platform had enhanced permeability for BBB and a longer retention time inside the brain in a healthy mouse model. Overall, the surface modification with zwitterionic polymer PMPC and cell-penetrating peptide TAT changes the circulation modality of the nanoparticles in vivo, and provides a promising pathway for BBB crossing as a potential drug delivery platform for CNS related disease therapy.

研究领域: 药学 · 纳米技术 · 神经科学 · 药物递送系统
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Materials Today Chemistry · 2022 · IF 7.613

Friction-induced supramolecular nanovalves for the potential treatment of osteoarthritis

Q. Wang,X. Yu,Y. Zhao,Y. Wang,K. Chen,Y. Liu,B. Wang,H. Zhang,Y. Sun

Owing to the overuse of rough articular cartilage, it increases the friction of joint and further leads to inflammation in joint cavities. However, the pathological changes also bring a new opportunity to achieve the treatment of osteoarthritis (OA). The increasing friction from damaged articular cartilage can convert more mechanical energy to heat. The higher localized temperature can reduce supramolecular interactions in general. Therefore, friction becomes another new activation to operate nanovalve systems for the targeting treatment of OA. Here, we designed and prepared a friction-induced nanovalve system constructed with β-cyclodextrins (β-CD)-modified mesoporous silica nanoparticles (MSN). Besides, a copolymer containing two components – guest molecules (adamantane, AD) and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) – has been self-assembled on the surface of β-CD-modified MSN (MSN-CD) by supramolecular host–guest interactions. In this design, the charged PMPC on the MSN surface can form a dense hydration layer by ion–dipole interactions, switch the friction from surfaces to water molecules to achieve hydration lubrication , and sharply reduce the coefficient of friction (COF). Besides, the higher localized temperature from the mechanical conversion can weaken the supramolecular host–guest interactions and turn on the nanovalves to accomplish the targeted release near rough articular cartilage of OA. Even when PMPC is peeled off, the hydrophilic surface of β-CD on MSN surface can still perform the acceptable lubricating properties. The following testings of cytotoxicity by CCK-8 and live/dead staining indicated the excellent biocompatibility. Further analysis of protein expression levels has also shown the potential application in OA.

CAS / MDL: 814-68-6 768-94-5
研究领域: 纳米技术 · 生物材料 · 药物递送系统 · 生物医学工程 · 骨科
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

Dual functional antifouling and bactericidal proteinaceous coating

Zhengge Wang,Chengyu Fu,Yingtao Gao,Zhaoji Wu,Weiqing Chen,Bowen Hu,Siqi Xu,Zhigang Zhang,Peng Yang

Coatings with both anti-fouling and bactericidal functions are used in many fields. In this work, lysozyme (Lyso) and poly (2-Methylallyloxyethyl phosphorylcholine) (PMPC) conjugate (Lyso-PMPC) is successfully designed and synthesized for the first time. A new nanofilm (PTL-PMPC) is then obtained by phase transition of lysozyme via the reduction of disulfide bonds in Lyso-PMPC. Benefit from lysozyme amyloid-like aggregates as surface anchors, the nanofilm shows excellent stability, it remains unchanged after treatment under extreme conditions such as ultrasonic and 3 M tape peeling. Due to the presence of zwitterionic polymer (PMPC) brush, the PTL-PMPC film has excellent antifouling properties against cell, bacterium, fungi, proteins, biofluids, phosphatide , polyose, esters, and carbohydrates. Meanwhile, the PTL-PMPC film is colourless and transparent. Further, a new coating (PTL-PMPC/PHMB) is fabricated by hybridizing PTL-PMPC with poly (hexamethylene biguanide) (PHMB). This coating had excellent antibacterial properties , and the antibacterial rate against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ) is more than 99.99%. In addition, the coating exhibit good hemocompatibility and low cytotoxicity.

研究领域: 材料科学 · 生物技术 · 生物材料 · 表面化学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2024 · IF 5.3

Panax notoginseng saponins and acetylsalicylic acid co-delivered liposomes for targeted treatment of ischemic stroke

Hao Cui,Yanchi Liu,Ying Yu,Dong Lv,Sha Ma,Mingju Gao,Ye Yang,Cheng Yuan,Yuan Liu,Chengxiao Wang

In this study, we aimed to develop brain-targeted co-delivery liposomes for the concurrent delivery of Panax notoginseng saponins (PNS) and acetylsalicylic acid (ASA) for the treatment of ischemic stroke. Within this system, PNS served as a cholesterol substitute, integrating into the phospholipid bilayer of the liposomes, while ASA was encapsulated internally. A poly-2-methacryloyloxyethyl phosphorylcholine (PMPC) polymer was synthesized and incorporated into the liposome surface. This formulation demonstrated an enhanced PNS-loading capacity and facilitated the synchronized delivery of key saponin components. Following PMPC modification, the liposomes exhibited prolonged circulation and improved transport across the blood–brain barrier (BBB) through acetylcholine receptor-mediated pathways. Furthermore, the co-delivery system exhibited enhanced therapeutic efficacy in a rat model of cerebral ischemia–reperfusion injury via the phosphoinositide 3-kinase/protein kinase C pathway. Additional analyses revealed significant effects on the metabolism of neurotransmitters, amino acids, folate, and various other pathways, indicating a multi-faceted therapeutic effect. Overall, this study presents an innovative research strategy for the comprehensive delivery of diverse components in traditional Chinese medicine formulations, highlighting the potential for synergistic treatments that combine traditional Chinese medicine with chemical agents.

研究领域: 药学 · 神经科学 · 中医药 · 药物递送系统 · 中风治疗
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Biomedical Materials · 2023 · IF 4

Grafting zwitterionic brushes from the surface of an epoxy-based transparent hydrogel for antifouling performance

Jiandong Han,Kexin Zhang,Qixing Cai,Peng Dong,Daping Quan,Ying Bai

Non-specific biofilm formation (biofouling) commonly occurs to the surface of biomedical devices, which causes infection to the human tissues and function loss after implantation. To enhance the antifouling properties on the bioinert hydrogel-based biomaterials, a novel surface grafting approach was developed using surface radical chain-transfer reaction mediated by DL-dithiothreitol (DTT), rather than catalyzed by cytotoxic metal ions. Zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brushes were grafted on the surface of poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate) (PHG) to obtain PHG-graft-PMPC (PHG-g-PMPC) hydrogel, which were shown to have tunable surface hydrophilicity while maintaining high water content and transparency. Elemental composition analysis and micromorphology demonstrated the success of surface grafting. Protein adhesion assays were carried out, showing the reduction of bovine serum albumin, lactoferrin, and lysozyme adhesion by ~ 90%, 80%, and 70%, respectively, compared to the pristine hydrogel. Significant resistance of bacterial attachment was observed on surface-modified hydrogel using gram-negative Escherichia coli and gram-positive Staphylococcus aureus, respectively. The PHG-g-PMPC hydrogel are potentially feasible in various biomedical applications, especially for preventing surface biofouling of ophthalmic implants and devices. Furthermore, this de novo approach provides a universal platform for surface functionalization via thiol-epoxy click chemistry and surface radical chain-transfer reaction.

研究领域: 生物材料 · 表面化学 · 生物医学工程 · 材料科学
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Bioactive Materials · 2024 · IF 18

Bioinspired super-hydrophilic zwitterionic polymer armor combats thrombosis and infection of vascular catheters

You Ke,Haotian Meng,Zeyu Du,Wentai Zhang,Qing Ma,Yuting Huang,Linxian Cui,Yifeng Lei,Zhilu Yang

Thrombosis and infection are two major complications associated with central venous catheters (CVCs), which significantly contribute to morbidity and mortality. Antifouling coating strategies currently represent an efficient approach for addressing such complications. However, existing antifouling coatings have limitations in terms of both duration and effectiveness. Herein, we propose a durable zwitterionic polymer armor for catheters. This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization, followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine (pMPC) via in-situ radical polymerization. The resulting pMPC coating armor exhibits super-hydrophilicity, thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro . In practical applications, the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model, as well as inhibited thrombus formation in a rabbit jugular vein model. Overall, our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.

研究领域: 生物材料 · 生物医学工程 · 聚合物科学 · 血栓研究 · 感染控制 · 医疗器械
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