Biomaterials最新文献

{"title":"Rapid and efficient immune response induced by a designed modular cholera toxin B subunit (CTB)-based self-assembling nanoparticle","authors":"Chao Pan ,&nbsp;Shujuan Yu ,&nbsp;Caixia Li ,&nbsp;Juntao Li ,&nbsp;Peng Sun ,&nbsp;Yan Guo ,&nbsp;Ting Li ,&nbsp;Dongshu Wang ,&nbsp;Kangfeng Wang ,&nbsp;Yufei Lyu ,&nbsp;Xiankai Liu ,&nbsp;Xiang Li ,&nbsp;Jun Wu ,&nbsp;Li Zhu ,&nbsp;Hengliang Wang","doi":"10.1016/j.biomaterials.2024.122946","DOIUrl":"10.1016/j.biomaterials.2024.122946","url":null,"abstract":"<div><div>Modular self-assembling nanoparticle vaccines, represent a cutting-edge approach in immunology with the potential to revolutionize vaccine design and efficacy. Although many innovative efficient modular self-assembling nanoparticles have been designed for vaccination, the immune activation characteristics underlying such strong protection remain poorly understood, limiting the further expansion of such nanocarrier. Here, we prepared a novel modular nanovaccine, which self-assembled via a pentamer cholera toxin B subunit (CTB) domain and an unnatural trimer domain, presenting <em>S.</em> Paratyphi A O-polysaccharide antigen, and investigated its rapid immune activation mechanism. The nanovaccine efficiently targets draining lymph nodes and antigen-presenting cells, facilitating co-localization with Golgi and endoplasmic reticulum. In addition, dendritic cells, macrophages, B cells, and neutrophils potentially participate in antigen presentation, unveiling a dynamic change of the vaccines in lymph nodes. Single-cell RNA sequencing at early stage and <em>i</em>N <em>vivo</em>/<em>i</em>N <em>vitro</em> experiments reveal its potent humoral immune response capabilities and protection effects. This nanoparticle outperforms traditional CTB carriers in eliciting robust prophylactic effects in various infection models. This work not only provides a promising and efficient candidate vaccine, but also promotes the design and application of the new type of self-assembled nanoparticle, offering a safe and promising vaccination strategy for infection diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122946"},"PeriodicalIF":12.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering M2 macrophage-derived exosomes modulate activated T cell cuproptosis to promote immune tolerance in rheumatoid arthritis","authors":"Guoquan Wu ,&nbsp;Tianyu Su ,&nbsp;Peng Zhou ,&nbsp;Rongze Tang ,&nbsp;Xu Zhu ,&nbsp;Jin Wang ,&nbsp;Minghao Chao ,&nbsp;Liying Fan ,&nbsp;Hanrong Yan ,&nbsp;Peng Ye ,&nbsp;Dehong Yu ,&nbsp;Fenglei Gao ,&nbsp;Hongliang Chen","doi":"10.1016/j.biomaterials.2024.122943","DOIUrl":"10.1016/j.biomaterials.2024.122943","url":null,"abstract":"<div><div>Nanomedicines for immune modulation have made advancements in the treatment of rheumatoid arthritis (RA). However, due to aberrations in patients' immune systems, inducing antigen-specific immune tolerance while halting disease progression remains a significant challenge. Here, we develop a highly targeted multifunctional nanocomplex, termed M2Exo@CuS-CitP-Rapa (M2CPR), with the aim of selectively inhibiting inflammatory immune reactions while promoting immune tolerance towards specific antigens. M2CPR specifically targets inflammatory tissues in RA, delivering CuS NPs, CitP, Rapa, and endogenous anti-inflammatory factors, thereby ameliorating the inflammatory joint microenvironment. CuS NPs induce Cuproptosis of activated T cells, whose fragments are engulfed by resident or recruited macrophages, resulting in abundant production of TGF-β. TGF-β acts synergistically with Rapa to induce the iDCs into tDCs. tDCs present CitP to Naive T cells, promoting Tregs differentiation. Tregs, in turn, produce more TGF-β, inducing tDCs differentiation, thereby establishing a cycle of immune tolerance. Through in vitro and in vivo experiments, we validate that M2CPR can induce robust and durable antigen-specific immune tolerance, offering a new paradigm for RA therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122943"},"PeriodicalIF":12.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming metabolic microenvironment for nerve regeneration via waterborne polylactic acid-polyurethane copolymer scaffolds","authors":"Yuan Feng ,&nbsp;Jinlin Chen ,&nbsp;Xiao Wang ,&nbsp;Chao Long ,&nbsp;Wenbo Wang ,&nbsp;Jingjing Lin ,&nbsp;Yuanyuan He ,&nbsp;Yanchao Wang ,&nbsp;Feng Luo ,&nbsp;Zhen Li ,&nbsp;Jiehua Li ,&nbsp;Hong Tan","doi":"10.1016/j.biomaterials.2024.122942","DOIUrl":"10.1016/j.biomaterials.2024.122942","url":null,"abstract":"<div><div>Cell metabolism, as the key driver of inflammation, revascularization and even subsequent tissue regeneration, is controlled by and also conversely influenced by signal transduction. Incorporation of cell metabolism into tissue engineering research holds immense potential for in-situ treatment repair and further understanding of the host-biomaterial cues in body response. In this study, an anti-inflammatory waterborne polyurethane scaffold incorporated with poly-<span>l</span>-lactic acid (PLLA) block was served to repair nerve injuries (LAx-WPU). Lactate was released through the degradation of LAx-WPU scaffolds, and the content increased with the addition of PLLA block over the degradation times. Thenceforth, the production of adenosine triphosphate (ATP) in primary neurons and neuronal axon growth were achieved by taking up lactate through monocarboxylate transporters (MCT2) for energy metabolism under glucose-free environment treated with LAx-WPU degradation solution. After LAx-WPU was implanted to repair brain nerve defects in rats, filamentous neurons elongation, rapid vascularization, and nerve tissue regeneration were realized up to 28 days with the positive expression of microtubule-associated protein (MAP2), β-tubulin (Tuj1), and platelet endothelial cell adhesion molecule (CD31) in the scaffolds. Results highlighted that the LAx-WPU scaffolds up-regulated not only the ATP-ADP-AMP purine metabolism compounds to mainly bridge neuroactive ligand-receptor interaction genes, cAMP pathway genes, and calcium pathway genes for neurocytes but also the ATP-GMP purine metabolism to angiogenesis in Gene Ontology (GO) analysis. Further analysis in reverse showed axonal regeneration is restrained by the inhibition of MCT2, proving LAx-WPU promoted nerve repair depended on lactate for energy. Therefore, LAx-WPU scaffolds construct an expected way to modulate the metabolic microenvironment for inducing nerve regeneration by intrinsic biomaterial metabolism cues without any bioactive factors.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122942"},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implantation of MSC spheroid-derived 3D decellularized ECM enriched with the MSC secretome ameliorates traumatic brain injury and promotes brain repair","authors":"Grace H. Chen ,&nbsp;Kee-Chin Sia ,&nbsp;Shao-Wen Liu ,&nbsp;Ying-Chi Kao ,&nbsp;Pei-Ching Yang ,&nbsp;Chia-Hsin Ho ,&nbsp;Shih-Chen Huang ,&nbsp;Peng-Ying Lee ,&nbsp;Min-Zong Liang ,&nbsp;Linyi Chen ,&nbsp;Chieh-Cheng Huang","doi":"10.1016/j.biomaterials.2024.122941","DOIUrl":"10.1016/j.biomaterials.2024.122941","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) presents substantial clinical challenges, as existing treatments are unable to reverse damage or effectively promote brain tissue regeneration. Although implantable biomaterials have been proposed to support tissue repair by mitigating the adverse microenvironment in injured brains, many fail to replicate the complex composition and architecture of the native extracellular matrix (ECM), resulting in only limited therapeutic outcomes. This study introduces an innovative approach by developing a mesenchymal stem cell (MSC) spheroid-derived three-dimensional (3D) decellularized ECM (dECM) that is enriched with the MSC-derived matrisome and secretome, offering a promising solution for TBI treatment and brain tissue regeneration. Proteomic and cytokine array analyses revealed that 3D dECM retained a diverse array of MSC spheroid-derived matrisome proteins and secretome components, which are crucial for replicating the complexity of native ECM and the therapeutic capabilities of MSCs. These molecules were found to underlie the observed effects of 3D dECM on immunomodulation, proneuritogenesis, and proangiogenesis in our <em>in vitro</em> functional assays. Implantation of 3D dECM into TBI model mice effectively mitigated postinjury tissue damage and promoted brain repair, as evidenced by a reduced brain lesion volume, decreased cell apoptosis, alleviated neuroinflammation, reduced glial scar formation, and increased of neuroblast recruitment to the lesion site. These outcomes culminated in improved motor function recovery in animals, highlighting the multifaceted therapeutic potential of 3D dECM for TBI. In summary, our study elucidates the transformative potential of MSC spheroid-derived bioactive 3D dECM as an implantable biomaterial for effectively mitigating post-TBI neurological damage, paving the way for its broader therapeutic application.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122941"},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bimetallic peroxide-based nanotherapeutics for immunometabolic intervention and induction of immunogenic cell death to augment cancer immunotherapy","authors":"Min Han ,&nbsp;Shiying Zhou ,&nbsp;Zunde Liao ,&nbsp;Chen Zishan ,&nbsp;Xiangting Yi ,&nbsp;Chuanbin Wu ,&nbsp;Dongmei Zhang ,&nbsp;Yao He ,&nbsp;Kam W. Leong ,&nbsp;Yiling Zhong","doi":"10.1016/j.biomaterials.2024.122934","DOIUrl":"10.1016/j.biomaterials.2024.122934","url":null,"abstract":"<div><div>Immunotherapy has transformed cancer treatment, but its efficacy is often limited by the immunosuppressive characteristics of the tumor microenvironment (TME), which are predominantly influenced by the metabolism of cancer cells. Among these metabolic pathways, the indoleamine 2,3-dioxygenase (IDO) pathway is particularly crucial, as it significantly contributes to TME suppression and influences immune cell activity. Additionally, inducing immunogenic cell death (ICD) in tumor cells can reverse the immunosuppressive TME, thereby enhancing the efficacy of immunotherapy. Herein, we develop CGDMRR, a novel bimetallic peroxide-based nanodrug based on copper-cerium peroxide nanoparticles. These nanotherapeutics are engineered to mitigate tumor hypoxia and deliver therapeutics such as 1-methyltryptophan (1MT), glucose oxidase (GOx), and doxorubicin (Dox) in a targeted manner. The design aims to alleviate tumor hypoxia, reduce the immunosuppressive effects of the IDO pathway, and promote ICD. CGDMRR effectively inhibits the growth of 4T1 tumors and elicits antitumor immune responses by leveraging immunometabolic interventions and therapies that induce ICD. Furthermore, when CGDMRR is combined with a clinically certified anti-PD-L1 antibody, its efficacy in inhibiting tumor growth is enhanced. This improved efficacy extends beyond unilateral tumor models, also affecting bilateral tumors and lung metastases, due to the activation of systemic antitumor immunity. This study underscores CGDMRR's potential to augment the efficacy of PD-L1 blockade in breast cancer immunotherapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122934"},"PeriodicalIF":12.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Procoagulant, antibacterial and antioxidant high-strength porous hydrogel adhesives in situ formed via self-gelling hemostatic microsheets for emergency hemostasis and wound repair","authors":"Yingli Shan ,&nbsp;Feng Cao ,&nbsp;Xin Zhao ,&nbsp;Jinlong Luo ,&nbsp;Haoliang Mei ,&nbsp;Limou Zhang ,&nbsp;Ying Huang ,&nbsp;Yutong Yang ,&nbsp;Liangruijie Yan ,&nbsp;Yayong Huang ,&nbsp;Yong Han ,&nbsp;Baolin Guo","doi":"10.1016/j.biomaterials.2024.122936","DOIUrl":"10.1016/j.biomaterials.2024.122936","url":null,"abstract":"<div><div>Procoagulant, antibacterial and analgesic hemostatic hydrogel dressing with high wet tissue adhesion, ultra-high burst pressure, and easy preparation shows huge promising for rapid hemostasis in emergencies, yet it remains a challenge. Herein, we propose hemostatic microsheets based on quaternized chitosan-g-gallic acid (QCS-GA) and oxidized hyaluronic acid (OHA), which merge the benefits of sponges, hydrogels, and powders for rapid hemostasis and efficient wound healing. Specifically, they exhibit a large specific surface area and excellent hydrophilicity, rapidly absorbing blood and self-gelling through electrostatic interaction and Schiff base crosslinking. And this results in dense, porous hydrogel adhesives with superior mechanical properties, adhesion strength, and ultra-high burst pressure. Furthermore, the microsheets are biocompatible, biodegradable, and possess procoagulant, antibacterial, and antioxidant properties. In mouse and rat liver hemorrhage models, the optimized formulation (QCS-GA + OHA4) demonstrated superior hemostatic effects compared to Celox. In particular, QCS-GA + OHA4 microsheets could stop bleeding quickly from rat femoral artery transection and deliver lidocaine to provide analgesia during emergency treatment. Additionally, they promoted wound healing in mouse full-thickness skin defect wound. These easy-to-manufacture hemostatic microsheets are adaptable to irregular wounds, providing a novel solution for rapid hemostasis and wound healing.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122936"},"PeriodicalIF":12.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rescue of mitochondrial dysfunction through alteration of extracellular matrix composition in barth syndrome cardiac fibroblasts","authors":"Janny Piñeiro-Llanes ,&nbsp;Silveli Suzuki-Hatano ,&nbsp;Ananya Jain ,&nbsp;Sree Venigalla ,&nbsp;Manasi Kamat ,&nbsp;Kari B. Basso ,&nbsp;William T. Cade ,&nbsp;Chelsey S. Simmons ,&nbsp;Christina A. Pacak","doi":"10.1016/j.biomaterials.2024.122922","DOIUrl":"10.1016/j.biomaterials.2024.122922","url":null,"abstract":"<div><div>Fibroblast-ECM (dys)regulation is associated with a plethora of diseases. The ECM acts as a reservoir of inflammatory factors and cytokines that mediate molecular mechanisms within cardiac cell populations. The role of ECM-mitochondria crosstalk in the development and progression of cardiac disorders remains uncertain. We evaluated the influence of ECM produced by stromal cells from patients with the mitochondrial cardiomyopathy (Barth syndrome, BTHS) and unaffected healthy controls on cardiac fibroblast (CF) metabolic function. To do this, cell-derived matrices CDMs were generated from BTHS and healthy human pluripotent stem cell-derived CFs (hPSC-CF) and used as cell culture substrates. BTHS CDMs negatively impacted the mitochondrial function of healthy hPSC-CFs while healthy CDMs improved mitochondrial function in BTHS hPSC-CFs. Mass spectrometry comparisons identified 5 matrisome proteins differentially expressed in BTHS compared to healthy CDM. Our results highlight a key role for the ECM in disease through its impact on mitochondrial function.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122922"},"PeriodicalIF":12.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose-primed PEEK orthopedic implants for antibacterial therapy and safeguarding diabetic osseointegration","authors":"Miaomiao He ,&nbsp;Hao Wang ,&nbsp;Qiuyang Han ,&nbsp;Xiuyuan Shi ,&nbsp;Shuai He ,&nbsp;Jiyu Sun ,&nbsp;Zhuoli Zhu ,&nbsp;Xueqi Gan ,&nbsp;Yi Deng","doi":"10.1016/j.biomaterials.2023.122355","DOIUrl":"10.1016/j.biomaterials.2023.122355","url":null,"abstract":"<div><p>Diabetic infectious microenvironment (DIME) frequently leads to a critical failure of osseointegration by virtue of its main peculiarities including typical hyperglycemia and pathogenic infection around implants. To address the plaguing issue, we devise a glucose-primed orthopedic implant composed of polyetheretherketone (PEEK), Cu-chelated metal-polyphenol network (hauberk coating) and glucose oxidase (GOx) for boosting diabetic osseointegration. Upon DIME, GOx on implants sostenuto consumes glucose to generate H₂O₂, and Cu liberated from hauberk coating catalyzes the H₂O₂ to highly germicidal •OH, which massacres pathogenic bacteria through photo-augmented chemodynamic therapy. Intriguingly, the catalytic efficiency of the coating gets greatly improved with the turnover number (TON) of 0.284 s⁻¹. Moreover, the engineered implants exhibit satisfactory cytocompatibility and facilitate osteogenicity due to the presence of Cu and osteopromotive polydopamine coating. RNA-seq analysis reveals that the implants enable to combat infections and suppress pro-inflammatory phenotype (M1). Besides, <em>in vivo</em> evaluations utilizing infected diabetic rat bone defect models at week 4 and 8 authenticate that the engineered implants considerably elevate osseointegration through pathogen elimination, inflammation dampening and osteogenesis promotion. Altogether, our present study puts forward a conceptually new tactic that arms orthopedic implants with glucose-primed antibacterial and osteogenic capacities for intractable diabetic osseointegration.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"303 ","pages":"Article 122355"},"PeriodicalIF":14.0,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72207592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cationic mesoporous silica nanoparticles alleviate osteoarthritis by targeting multiple inflammatory mediators","authors":"Tongfei Shi ,&nbsp;Jingtong Zhao ,&nbsp;Kongrong Long ,&nbsp;Mohan Gao ,&nbsp;Fangman Chen ,&nbsp;Xuenian Chen ,&nbsp;Yue Zhang ,&nbsp;Baoding Huang ,&nbsp;Dan Shao ,&nbsp;Chao Yang ,&nbsp;Liang Wang ,&nbsp;Ming Zhang ,&nbsp;Kam W. Leong ,&nbsp;Li Chen ,&nbsp;Kan He","doi":"10.1016/j.biomaterials.2023.122366","DOIUrl":"10.1016/j.biomaterials.2023.122366","url":null,"abstract":"<div><p>Osteoarthritis (OA) is a common and complex inflammatory disorder that is frequently compounded by cartilage degradation, synovial inflammation, and osteophyte formation. Damaged chondrocytes release multiple danger mediators that exacerbate synovial inflammation and accelerate the progression to OA. Conventional treatments targeting only a single mediator of OA have failed to achieve a strong therapeutic effect. Addressing the crucial role of multiple danger mediators in OA progression, we prepared polyethylenimine (PEI)-functionalized diselenide-bridged mesoporous silica nanoparticles (MSN-PEI) with cell-free DNA (cfDNA)-binding and anti-oxidative properties. In models of surgery-induced and collagenase-induced arthritis, we showed that these cationic nanoparticles attenuated cartilage degradation and provided strong chondroprotection against joint damage. Mechanistically, multiple target blockades alleviated oxidative stress and dampened cfDNA-induced inflammation by suppressing the M1 polarization of macrophages. This study suggests a beneficial direction for targeting multiple danger mediators in the treatment of intractable arthritis.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"303 ","pages":"Article 122366"},"PeriodicalIF":14.0,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72207591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An SS31-rapamycin conjugate via RBC hitchhiking for reversing acute kidney injury","authors":"Bohong Yu ,&nbsp;Yubo Liu ,&nbsp;Yingxi Zhang ,&nbsp;Linyi Xu ,&nbsp;Kai Jin ,&nbsp;Andi Sun ,&nbsp;Xiuli Zhao ,&nbsp;Yongjun Wang ,&nbsp;Hongzhuo Liu","doi":"10.1016/j.biomaterials.2023.122383","DOIUrl":"10.1016/j.biomaterials.2023.122383","url":null,"abstract":"<div><p>Mitochondrial dysfunction plays a major role in driving acute kidney injury (AKI) via alteration in energy and oxygen supply, which creates further ROS and inflammatory responses. However, mitochondrial targeting medicine in recovering AKI is challenging. Herein, we conjugated SS31, a mitochondria-targeted antioxidant tetrapeptide connecting a cleavable linker to rapamycin (Rapa), which provided specific interaction with FK506-binding protein (FKBP) in the RBCs. Once entering the bloodstream, SS31-Rapa could be directed to the intracellular space of RBCs, allowing the slow diffusion of the conjugate to tissues via the concentration gradient. The new RBC hitchhiking strategy enables the encapsulation of conjugate into RBC via a less traumatic and more natural and permissive manner, resulting in prolonging the t_1/2 of SS31 by 6.9 folds. SS31-Rapa underwent the direct cellular uptake, instead of the lysosomal pathway, released SS31 in response to activated caspase-3 stimulation in apoptotic cells, favoring the mitochondrial accumulation of SS31. Combined with autophagy induction associated with Rapa, a single dose of SS31-Rapa can effectively reverse cisplatin and ischemia reperfusion-induced AKI. This work thus highlights a simple and effective RBC hitchhiking strategy and a clinically translatable platform technology to improve the outcome of other mitochondrial dysfunctional related diseases.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"303 ","pages":"Article 122383"},"PeriodicalIF":14.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71519863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}