NANOTECHNOLOGY
·
2021
·Vol. 33
·期 8
·085103
·
IF 3.874
Xiuli Zhang,Ruqing Gao,Huiyu Yan,Zijian Zhao,Jun Zhang,Weiming You
Bcl-2, an anti-apoptotic protein, is always overexpressed in tumor cells to suppress the pro-apoptotic function of Bax, thereby prolonging the life of the tumor. However, BH3 proteins could directly activate Bax via antagonizing Bcl-2 to induce apoptosis in response to the stimulation. Thus, mimicking BH3 proteins with a peptide is a potential strategy for anti-cancer therapy. Unfortunately, clinical translation of BH3-mimic peptide is hindered by its inefficacious cellular internalization and proteolysis resistance. Herein, we translated a BH3-mimic peptide into a peptide-auric spheroidal nanocluster (BH3-AuNp), in which polymeric BH3-Auric precursors [Au1+-S-BH3]n are in situ self-assembled on the surface of gold nanoparticles by a one-pot synthesis. Expectedly, this strategy could improve the anti-proteolytic ability and cytomembrane penetrability of the BH3 peptide. As a result, BH3-AuNp successfully induced the apoptosis of two cancer cell lines by an order of magnitude compared to BH3. This therapeutic and feasible peptide nano-engineering strategy will help peptides overcome the pharmaceutical obstacles, awaken its biological functions, and possibly revive the research about peptide-derived nanomedicine.
研究领域:
生物化学
·
纳米医学
·
肿瘤学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 21
·4677-4683
·
IF 7
Xiuxia Sun,Siqi Quan,Bo Wang,Qi Wang,Wenhua Li,Jianxi Xiao
Collagen is the most abundant protein in various connective tissues, providing mechanical integrity as well as regulating cellular activities. Self-assembled peptides have been extensively explored to develop collagen mimetic materials, due to their attractive features such as easy synthesis, selective sequences and low immunogenicity. Metal ion-triggered self-assembly of collagen mimetic peptides has recently received increasing interests, since the addition of external stimuli offers programmable control of the self-assembly process. We have for the first time reported a peptide-stimulated self-assembly of collagen mimetic peptides into nanospheres by electrostatic interaction and π–π stacking. We have accidentally discovered that FAM-modified positively-charged triple helical peptide FAM-PRG was highly soluble, while the addition of a single-stranded negatively-charged peptide EOG-10 efficiently drove its self-assembly into well-ordered spherical nanomaterials. Peptide EOG-10 has been shown to mediate similar self-assembly of TPE-modified triple-helical peptide TPE-PRG into luminescent exquisite nanospheres, consistently demonstrating the robustness of this peptide-triggered strategy. Fluorescence monitoring of the interaction of EOG-10 and TPE-PRG at different ratios indicated that EOG-10 specifically binds to TPE-PRG to form a 3 : 1 complex. High salt concentration was shown to inhibit the self-assembly of TPE-PRG with EOG-10, suggesting that their self-assembly was controlled by electrostatic interaction. The self-assembly of TPE-PRG with EOG-10 has been further revealed to require the exact lengths of both peptides as well as complementary sequences without mutations, indicating a pairwise “side-by-side” binding mode. Notably, the identity of the N-terminal residues of X-PRG has been found to play a determinant role in the self-assembly, while non-aromatic residues lost the self-assembling capability, suggesting that π–π stacking and electrostatic interactions collectively modulate the self-assembly of X-PRG and EOG-10. To conclude, we have developed a highly biocompatible and programmably controlled peptide-triggered self-assembly approach to create novel collagen mimetic nanomaterials, which may have great potential in advanced functional materials.
研究领域:
生物材料学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 8
·2212-2226
·
IF 6.183
Xue Feng,Tong Zhou,Peifang Xu,Juan Ye,Zhongru Gou,Changyou Gao
Due to the poor self-repair capabilities of articular cartilage, chondral or osteochondral injuries are difficult to be recovered. In this study, an N-cadherin mimetic peptide sequence HAVDIGGGC (HAV) was conjugated to direct cell–cell interactions, and an aggrecanase-1 cleavable peptide sequence CRDTEGE-ARGSVIDRC (ACpep) was used to crosslink hyperbranched PEG-based multi-acrylate polymer (HBPEG) with cysteamine-modified chondroitin sulfate (Cys-CS), obtaining an aggrecanase-1 responsively degradable and HAV-conjugated hydrogel ((HAV-HBPEG)-CS-ACpep). A HBPEG-CS-ACpep hydrogel without the HAV motif was also prepared. The two hydrogels exhibited similar equilibrium swelling ratios, elastic moduli and pore sizes after lyophilization, indicating the negligible influence of conjugated HAV on the crosslinking networks and mechanical properties of the hydrogels. After being degraded in PBS, aggrecanase-1 (ADAMTS4) and trypsin, the HBPEG-CS-ACpep hydrogel exhibited significantly decreased elastic moduli with a much lower value when incubated in enzyme solutions. The two hydrogels could maintain the viability of encapsulated bone marrow-derived mesenchymal stem cells (BMSCs), and the (HAV-HBPEG)-CS-ACpep hydrogel better promoted the cell–cell interactions. After being implanted into osteochondral defects in rabbits for 18 weeks, the two cell-laden hydrogel groups achieved better repair effects than the blank control group. Moreover, hyaline cartilage was formed in the (HAV-HBPEG)-CS-ACpep/BMSCs hydrogel group, while a hybrid of hyaline cartilage and fibrocartilage was found in the HBPEG-CS-ACpep/BMSCs hydrogel group.
研究领域:
组织工程
·
再生医学
·
生物材料
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DOI
PubMed
高影响因子
COMPOSITES SCIENCE AND TECHNOLOGY
·
2016
·
IF 3.897
Ting Kang,Xiaoli Hua,Peiqing Liang,Minyu Rao,Qin Wang,Changyun Quan,Chao Zhang,Qing Jiang
To be better used as implant materials in bone regeneration, bioactivity and osteogenesis of poly(methyl methacrylate) (PMMA)-based bone cement need to be further enhanced. In this study, bioactive hydroxyapatite (HA) nanoparticle decorated with polydopamine (pDA) and BMP2 mimicking peptide (serine-serine-valine-proline-threonine, SSVPT) was incorporated into PMMA-based cement (p x -HA/PMMA). The presence of pDA layer on HA surface could keep the mechanical property of p x -HA/PMMA cements comply with the requirement of clinical application. More importantly, the p x -HA/PMMA cement exhibited excellent biomechanical property with enhanced interfacial adhesion between cement and swine femur. Biomineralization and cell experiment in vitro showed that the incorporation of pDA-coated HA and SSVPT can synergistically enhance the bioactivity of p x -HA/PMMA cement for regeneration and provide an attractive strategy to reconstruction of load-bearing bone.
研究领域:
生物材料学
·
骨再生医学
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产品关联
DOI
高影响因子
CHEMISTRY OF MATERIALS
·
2025
·
IF 7
Jia Kong,Jiaxing Zhang,Yirui Zhang,Huanxin Xue,Xin Guo,Nan Wang,Ziyi Gao,Menghuan Sun,Yinqiang Xia,Yuefei Wang,Hao Ren,Peng Yang,Man Shing Wong
Amyloid β (Aβ) aggregates are a neuropathological hallmark of Alzheimer’s disease (AD). Despite being a prime therapeutic target, past Aβ-targeted trials have primarily focused on its hydrophobic core, yielding unsatisfactory results. In this study, we aligned the structural features of Aβ42 filaments and found that the hydrophobic core and C-terminal region show notable similarities, and the N-terminal region exhibits considerable disorder. Through residue substitution studies, we identified the His13-His14 motif at the disorder–order boundary as particularly effective in mitigating Aβ42’s fibrillation pathway and neurotoxicity, alongside the Phe19-Phe20 hydrophobic core, presenting a promising target for therapeutic intervention. We then designed a series of peptide mimetics based on these Aβ features. Among them, peptide mimetic III, with the sequence of Phe-His-His, exhibited an assembly of antiparallel β-sheet structures primarily driven by hydrogen bonding, showcasing favorable rheological properties and biosafety. Interestingly, mimetic III predominantly patches the N-terminal region of Aβ42 fibrils through hydrogen bond-dominated interactions, effectively modulating aggregation and neurotoxicity in a “like-interacts-with-like” manner. Furthermore, mimetic III eliminates the risk of Aβ42 aggregating into neurotoxic intermediates, rescuing both human and mouse-derived neuronal cells from Aβ42-induced toxicity. Our study demonstrated that peptide mimetics targeting the N-terminal region of Aβ42 is a promising alternative for modulating amyloidosis-related neurotoxicity.
研究领域:
神经生物学
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分子药理学
·
蛋白质聚集疾病
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转化医学
·
神经退行性疾病
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 44
·8770-8779
·
IF 4.543
Jiachen Sun,Yanxia Zhang,Bin Li,Yong Gu,Liang Chen
Stimulating the adhesion and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is crucial for the scaffold materials used in bone tissue engineering. In this study, a silk fibroin (SF)/nano-hydroxyapatite (nHAp) scaffold was prepared, embedded with SF microspheres containing bone morphogenetic protein-2 (BMP-2) and surface-modified through chemical conjugation with the type I collagen-mimetic peptide GFOGER. Surface-bound GFOGER and sustained BMP-2 release promoted the adhesion and osteogenic differentiation, respectively, of BMSCs. Our results indicated that this system released low doses of BMP-2 in a sustained manner, thereby avoiding cost and safety problems. The biological responses to this scaffold were investigated both in vitro and in vivo. Our results indicated that the synergistic effect of GFOGER and BMP-2 promoted the adhesion and osteogenic differentiation of BMSCs, thus leading to complete bone bridging of rat cranial defects after 12 weeks of implantation. This system might provide a powerful platform for treating bone defects and for bone tissue engineering.
研究领域:
组织工程
·
生物医用材料
·
再生医学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2020
·
IF 10.257
Shengfeng Huang,Rentao Tang,Tingting Zhang,Jing Zhao,Zhengjin Jiang,Qiqin Wang
In this study, a high-performance anti-fouling coating based on poly adenine (polyA n ) as well as a highly specific cluster of differentiation 20 (CD20) epitope mimetic peptide (CN14) were employed to synergistically construct a facile biosensor for the rapid and sensitive determination of rituximab in lymphoma patients' plasma. The well-designed and optimized polyA n coating displayed excellent stability, hydrophilicity , thanks to its intrinsic affinity with gold surface and thoroughly exposed hydrophilic phosphate groups. Moreover, the proposed strategy avoids the necessity to modify binding groups (e.g. thiol), making it more facile, repeatable and efficient. When dealing with complex clinical plasma samples, the polyA n coating demonstrated better anti-fouling performance and lower background signal in comparison with mercaptan and bovine serum albumin coatings. The dissociation constant (~60 nM) between CN14 and rituximab was measured by microscale thermophoresis and their binding mechanism was further explained using computer simulation. The constructed GE/CN14/polyA 20 biosensor displayed satisfactory performance with detection limit of 35.26 ng/mL. Finally, the proposed biosensor was successfully applied for rapidly determining rituximab in lymphoma patients' plasma, and exhibited comparable accuracy to the commercial ELISA , but has advantages including a shorter detection time, wider detection range and lower cost. It's worth noting that the anti-fouling polyA n coating can be tailored according to the surface property of sensing interface and can be easily expanded to other gold electrode related biosensors.
研究领域:
生物医学工程
·
临床化学
·
生物传感器
·
癌症研究
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DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Fei Li,Chuwei Zhang,Xiaoping Zhong,Bo Li,Mengnan Zhang,Wanqian Li,Lifei Zheng,Xinghua Zhu,Shixuan Chen,Yi Zhang
Diabetic foot ulcers, pressure ulcers, and bedsores can easily develop into chronic wounds with bacterial infections, complicating wound healing. This work reports a two-step strategy for treating infected chronic wounds. Firstly, LL37 mimetic peptide-W379 peptides were rapidly released to eliminate the bacterial biofilm on the wound. Then, 3D radially aligned nanofiber scaffolds loaded with W379 antimicrobial peptide and PDGF-BB were used to treat the wound to prevent bacterial infection recurrence and promote angiogenesis and granulation tissue regeneration, thereby accelerating wound healing. In the presented study, we found that the combined use of burst and controlled release of W379 antimicrobial peptide effectively clears the bacterial biofilm and prevents the recurrence of bacterial infection. Additionally, we found that the removal of the bacterial biofilm contributed to modulating the local inflammatory response from a pro-inflammatory type to a pro-regenerative type. Furthermore, the use of PDGF-BB significantly promotes neovascularization and granulation tissue regeneration in the wound bed, resulting in accelerating re-epithelialization and wound closure. Our study provides a promising treatment method for the repair of infected chronic wounds.
研究领域:
生物医学工程
·
伤口愈合
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组织工程
·
感染控制
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2023
·
IF 14.5
Jiawen Yang,Aixuan Zhou,Minyi Li,Qiaoxian He,Jingwei Zhou,Jacques Crommen,Wentao Wang,Zhengjin Jiang,Qiqin Wang
Due to low immobilized ligand density, limited binding capacity, and severe interference from serum proteins, developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge. In this study, mimotope peptide modified pompon mum-like biomimetic magnetic microparticles (MMPs, 3.8 μm) that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time. Benefit from the numerous ligand binding sites (Ni 2+ ) on the pompon mum-like MMPs, these novel materials achieved ≥10 times higher peptide ligand densities (>2300 mg/g) and antibody binding capacities (1380 mg/g) compared to previous reported biomaterials. Leveraging the high specificity of the mimotope peptide, rituximab can be precisely recognized and enriched from cell culture media or serum samples. We also established an LC‒MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum. Intriguingly, deamidation of Asn55 and Asn33, as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab, which could potentially influence antibody function and require careful monitoring. Overall, these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies, offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.
研究领域:
生物技术
·
药学
·
分析化学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jinlong Qin,Min Sun,Jiajing Cheng,Huici Jiang,Mingchen Lv,Jianxing Jing,Ran Chen,Zhen Fan,Jianzhong Du
Unavoidable damage to the basal layer of the endometrium has a huge negative impact on a woman’s reproductive health and menstrual cycle. However, it is difficult for medicine to penetrate a series of biological barriers toward the basal layer in the deeper area of the endometrium. To meet this challenge, we developed an ultrasound-responsive hydrogel incorporated with a transforming growth factor-beta (TGF-β) mimetic peptide to enhance pregnancy outcomes by restoring the function of a wounded endometrium due to its deep-tissue-penetration capability. In vitro studies revealed that the TGF-β-mimetic-peptide-loaded hydrogel could achieve 64.35% of cell migration under ultrasound stimulation even in phosphate-buffered saline of pH 6.0. Upon in situ sonication at the uterus, carboxymethyl chitosan can be released from degraded hydrogel to open tight junctions with reduced interstitial pressure by ultrasound to promote deep penetration. Rat studies revealed that the penetration capability of TGF-β-mimetic-peptide-loaded hydrogel with sonication was 1.6 times higher than that of the control group. Besides the rat uterine model, ex vivo human uterine tissue was also collected and imaged, demonstrating up to ∼700 μm of tissue penetration depth. In addition, compared to control groups, effective uterus recovery without intrauterine stenosis and endometrial cavity fluid was observed from rats with severe uterine injury treated by TGF-β-mimetic-peptide-loaded hydrogel. In addition, fertility restoration in the endometrial injury model was observed after treatment with such an ultrasound-responsive hydrogel incorporated with TGF-β mimetic peptides. Overall, this work provides an effective approach to treating endometrial injury for enhanced pregnancy outcomes.
研究领域:
生物医学工程
·
生殖医学
·
组织工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Shengfeng Huang,Weida Wang,Jiamin Li,Tingting Zhang,Yang Liang,Qiqin Wang,Zhengjin Jiang
The sensitive, accurate and fast monitoring of therapeutic drugs plays an important role in guiding clinical medication or individualized treatment. Inspired by the highly efficient interactions of ordered structures in living organisms, a multifunctional DNA mediated spatially confined assembly (SCA) based antibody orientation strategy was proposed in this work. The multifunctional DNA containing a signaling molecule labeled on the head and a poly adenine tail (20 bases), can not only direct the ordered immobilization of antibodies on gold nanoparticles, but can also enrich electrochemical signal molecules. Compared with a randomly arranged antibody immobilization strategy, the SCA based antibody orientation strategy can produce nearly 200% of peak current signal. Moreover, MoS 2 /gold nanoparticles were used to modify electrodes in this study in order to improve the electrochemically active surface area and electron transfer of the electrode as well as the spatial regulation of thiol peptides. By using a highly specific CD20 epitope mimetic peptide this proposed biosensor exhibits high sensitivity for rituximab detection (LOD 56.4 fM) as well as good selectivity, stability and satisfactory accuracy. When applying it for detecting rituximab in lymphoma patients’ plasma, comparable results to commercial ELISA were obtained with a low RSD (＜6.5%). The proposed signal tag fabrication strategy could easily be extended to analyze other targets by changing the sensing platform, which has a potential application in the fields of biological analysis and medical diagnosis.
研究领域:
生物传感器
·
纳米技术
·
电化学
·
药物监测
·
医学诊断
✓ 已验证
DOI
高影响因子
COMPOSITES PART B-ENGINEERING
·
2024
·
IF 12.7
Weiguang Zhao,Yin Yang,Yutong Liu,Yang Wu,Renjie Wang,Shiyi Cao,Haoxin Cai,Zijie Xu,Jun Fang,Hongbing Deng,Zhihong Liu
The complications of enterocystoplasy have challenged traditional bladder reconstruction methods. Tissue engineering scaffolds, involving stem cells implantation and vascularization strategies, emerge as promising alternatives. However, their applications are hindered by issues regarding the source of stem cells and the rapid loss of bioactive factors in a urinary environment. Here, a multilayer biomimetic scaffold consisting of polycaprolactone (PCL) nanofibrous mats and oxidized dextran/carboxymethyl chitosan hydrogel has been synthesized. Bone marrow homing peptide (BMHP) and vascular endothelial growth factor-mimicking peptide (VP) were incorporated into the hydrogel to recruit endogenous stem cells and promote vascularization, respectively. The results indicated that PCL mats not only reinforced the mechanical properties of composite scaffolds but also prolonged the retention of peptides via the hydrophobic surface. In vivo experiments demonstrated that BMHP and VP had crosstalk effects, amplifying their functions to accelerate bladder regeneration, enhance contractility of smooth muscle cells, inhibit fibrosis, and improve innervation. Overall, the novel functionalized scaffolds are potentially viable for urologic tissue reconstruction.
研究领域:
组织工程
·
再生医学
·
生物材料
·
泌尿外科
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）