Pub Date : 2026-04-01Epub Date: 2026-01-13DOI: 10.1016/j.mtbio.2026.102803
Yang Chen , Longcai Liu , Xiaojuan Hu , Yilin Huang , Shijie Yao , Lichen Ji , Hai Zou , Xiaozhou Mou , Yu Cai
Although immunotherapy has achieved impressive breakthroughs in head and neck squamous cell carcinoma (HNSCC), it still encounters significant challenges such as the intrinsic low immunogenicity microenvironment and limited T cell infiltration. In this work, we aimed to edit the CD274 gene of HNSCC cells by optogenetics with second near-infrared (NIR-II) light, thereby reducing the CD274 expression and improving the efficacy of photo-immunogenic therapy. Specifically, a biomimetic nanoplatform (ARPC) was established by using an α-LDLR (low density lipoprotein receptor antibody) engineered red blood cell membrane (RBCm) to deliver NIR-II photothermal polymers and CRISPR/Cas9 plasmids. After intravenous injection into HNSCC-bearing mice, ARPC can induce heat stress upon NIR-II laser irradiation at tumor sites, causing the upregulation of Hsp70 to trigger CRISPR/Cas9 for CD274 editing. Moreover, the mild photothermal therapeutic effect of ARPC simultaneously induced immunogenic cell death in tumor cells for enhancing CD8+ T cell infiltration and proliferation, and thereby leading to photoimmunotherapy. This study provides an NIR-II optogenetic CRISPR/Cas9 CD274 for editing reprogrammed photo-immunogenic therapy strategy, showing great clinical potential for overcoming the low immunogenicity of HNSCC.
{"title":"NIR-II biomimetic nanoplatform optogenetic CD274 editing of HNSCC immunogenicity for enhanced photoimmunotherapy","authors":"Yang Chen , Longcai Liu , Xiaojuan Hu , Yilin Huang , Shijie Yao , Lichen Ji , Hai Zou , Xiaozhou Mou , Yu Cai","doi":"10.1016/j.mtbio.2026.102803","DOIUrl":"10.1016/j.mtbio.2026.102803","url":null,"abstract":"<div><div>Although immunotherapy has achieved impressive breakthroughs in head and neck squamous cell carcinoma (HNSCC), it still encounters significant challenges such as the intrinsic low immunogenicity microenvironment and limited T cell infiltration. In this work, we aimed to edit the CD274 gene of HNSCC cells by optogenetics with second near-infrared (NIR-II) light, thereby reducing the CD274 expression and improving the efficacy of photo-immunogenic therapy. Specifically, a biomimetic nanoplatform (ARPC) was established by using an α-LDLR (low density lipoprotein receptor antibody) engineered red blood cell membrane (RBCm) to deliver NIR-II photothermal polymers and CRISPR/Cas9 plasmids. After intravenous injection into HNSCC-bearing mice, ARPC can induce heat stress upon NIR-II laser irradiation at tumor sites, causing the upregulation of Hsp70 to trigger CRISPR/Cas9 for CD274 editing. Moreover, the mild photothermal therapeutic effect of ARPC simultaneously induced immunogenic cell death in tumor cells for enhancing CD8<sup>+</sup> T cell infiltration and proliferation, and thereby leading to photoimmunotherapy. This study provides an NIR-II optogenetic CRISPR/Cas9 CD274 for editing reprogrammed photo-immunogenic therapy strategy, showing great clinical potential for overcoming the low immunogenicity of HNSCC.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102803"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024353","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}
Pub Date : 2026-04-01Epub Date: 2026-01-29DOI: 10.1016/j.mtbio.2026.102834
Xun-Zheng Su , En-Qi Qiao , Wen-Yu Wu , Yue-Ran Chen , Yan Li , Jin-Hua Song , Xue-Hao Wang , Guo-Qiang Shao , Gao-Jun Teng , Fei Xiong
Embolization is an effective treatment modality for intermediate- and advanced-stage Hepatocellular carcinoma (HCC). Transarterial radioembolization (TARE), which combines radiotherapy with embolization, not only induces tumor necrosis by occluding blood flow with embolic agents but also exerts local radiotherapeutic effects to damage tumor cells, thereby significantly enhancing the therapeutic efficacy of embolization. Current radiolabeled microspheres used for internal irradiation therapy in HCC have limitations, such as suboptimal embolization efficacy, a tendency for non-target embolization, an inability to track embolic agents during and after surgery, and the generation of reactive oxygen species (ROS) during radiotherapy, which can damage normal tissues. To address these issues, visualizable cationic quaternary ammonium salt-based drug-eluting microspheres capable of loading 131I and the radioprotective agent amifostine were developed. The microspheres exhibit good embolic properties and can be visualized over an extended period using CT and DSA. The microspheres, carrying a positive charge, are capable of loading amifostine via ion exchange. After loading amifostine, these microspheres can not only provide local radiotherapy within the tumor but also continuously release amifostine locally to neutralize ROS in normal liver tissue. This approach not only enhances the utilization of amifostine in vivo but also protects the liver without compromising the efficacy of TARE thereby further improving the precision of radiotherapy.
{"title":"Radioprotectant-loaded visualizable cationic radioactive microspheres: Reduced hepatic tissue damage and intra/postoperative imaging during TARE","authors":"Xun-Zheng Su , En-Qi Qiao , Wen-Yu Wu , Yue-Ran Chen , Yan Li , Jin-Hua Song , Xue-Hao Wang , Guo-Qiang Shao , Gao-Jun Teng , Fei Xiong","doi":"10.1016/j.mtbio.2026.102834","DOIUrl":"10.1016/j.mtbio.2026.102834","url":null,"abstract":"<div><div>Embolization is an effective treatment modality for intermediate- and advanced-stage Hepatocellular carcinoma (HCC). Transarterial radioembolization (TARE), which combines radiotherapy with embolization, not only induces tumor necrosis by occluding blood flow with embolic agents but also exerts local radiotherapeutic effects to damage tumor cells, thereby significantly enhancing the therapeutic efficacy of embolization. Current radiolabeled microspheres used for internal irradiation therapy in HCC have limitations, such as suboptimal embolization efficacy, a tendency for non-target embolization, an inability to track embolic agents during and after surgery, and the generation of reactive oxygen species (ROS) during radiotherapy, which can damage normal tissues. To address these issues, visualizable cationic quaternary ammonium salt-based drug-eluting microspheres capable of loading <sup>131</sup>I and the radioprotective agent amifostine were developed. The microspheres exhibit good embolic properties and can be visualized over an extended period using CT and DSA. The microspheres, carrying a positive charge, are capable of loading amifostine via ion exchange. After loading amifostine, these microspheres can not only provide local radiotherapy within the tumor but also continuously release amifostine locally to neutralize ROS in normal liver tissue. This approach not only enhances the utilization of amifostine in vivo but also protects the liver without compromising the efficacy of TARE thereby further improving the precision of radiotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102834"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165333","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}
Pub Date : 2026-04-01Epub Date: 2026-02-03DOI: 10.1016/j.mtbio.2026.102892
Zelong Jiang , Hong Huang , Mengqi Zhang , Feng Lin , Guchun Qin , Niqiang Zhou , Guanhua Qiu , Jie Chen , Duo Wang , Yunxi Huang , Chang Zhao
Magnetic hyperthermia therapy (MHT) has emerged as a promising anti-cancer strategy due to its precise spatial controllability and immune-activating effects. However, tumor cells can rapidly develop thermotolerance through the upregulation of heat shock proteins (HSPs), activation of the NF-κB signaling pathway, and recruitment of immunosuppressive cells, etc. Herein, we design a tumor cell membrane coated H2S-releasing magnetic nanoplatform (CmMN@ADT) to overcome this resistance. This nanoplatform was synthesized by coordinating Fe3O4 nanoparticles with 1,3,5-benzenetricarboxylic acid (BTC) to form a magnetic metal organic framework (Fe3O4@MIL-100, MN), which was subsequently loaded with the H2S donor ADT-OH and coated with tumor cell membranes for homotypic targeting. Upon exposure to an alternating magnetic field (AMF), the Fe3O4@MIL-100 core enables localized hyperthermia, while acidic tumor microenvironment triggers ADT-OH release for sustained H2S generation. The released H2S enhances tumor cell sensitivity to hyperthermia by inhibiting NF-κB activation and downregulating HSP expression. Suprisingly, H2S can also augment the MN induced ferroptosis. In vitro and in vivo studies have demonstrated that CmMN@ADT effectively induces tumor ablation and elicits potent anti-tumor immune responses, ultimately achieving the inhibition of the growth of both primary and metastatic tumors. Collectively, this study presents a novel H2S driven magnetic MOF nanoplatform that achieves dual mode synergy between H2S Augmented MHT and ferroptosis, providing a mechanistically guided strategy to overcome tumor thermotolerance and achieve durable tumor suppression.
{"title":"A biomimetic magnetic MOF-based nanoplatform for H2S-mediated thermal re-sensitization and immune reprogramming in multimodal hyperthermia therapy","authors":"Zelong Jiang , Hong Huang , Mengqi Zhang , Feng Lin , Guchun Qin , Niqiang Zhou , Guanhua Qiu , Jie Chen , Duo Wang , Yunxi Huang , Chang Zhao","doi":"10.1016/j.mtbio.2026.102892","DOIUrl":"10.1016/j.mtbio.2026.102892","url":null,"abstract":"<div><div>Magnetic hyperthermia therapy (MHT) has emerged as a promising anti-cancer strategy due to its precise spatial controllability and immune-activating effects. However, tumor cells can rapidly develop thermotolerance through the upregulation of heat shock proteins (HSPs), activation of the NF-κB signaling pathway, and recruitment of immunosuppressive cells, etc. Herein, we design a tumor cell membrane coated H<sub>2</sub>S-releasing magnetic nanoplatform (CmMN@ADT) to overcome this resistance. This nanoplatform was synthesized by coordinating Fe<sub>3</sub>O<sub>4</sub> nanoparticles with 1,3,5-benzenetricarboxylic acid (BTC) to form a magnetic metal organic framework (Fe<sub>3</sub>O<sub>4</sub>@MIL-100, MN), which was subsequently loaded with the H<sub>2</sub>S donor ADT-OH and coated with tumor cell membranes for homotypic targeting. Upon exposure to an alternating magnetic field (AMF), the Fe<sub>3</sub>O<sub>4</sub>@MIL-100 core enables localized hyperthermia, while acidic tumor microenvironment triggers ADT-OH release for sustained H<sub>2</sub>S generation. The released H<sub>2</sub>S enhances tumor cell sensitivity to hyperthermia by inhibiting NF-κB activation and downregulating HSP expression. Suprisingly, H<sub>2</sub>S can also augment the MN induced ferroptosis. In vitro and in vivo studies have demonstrated that CmMN@ADT effectively induces tumor ablation and elicits potent anti-tumor immune responses, ultimately achieving the inhibition of the growth of both primary and metastatic tumors. Collectively, this study presents a novel H<sub>2</sub>S driven magnetic MOF nanoplatform that achieves dual mode synergy between H<sub>2</sub>S Augmented MHT and ferroptosis, providing a mechanistically guided strategy to overcome tumor thermotolerance and achieve durable tumor suppression.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102892"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170414","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}
Pub Date : 2026-04-01Epub Date: 2026-01-31DOI: 10.1016/j.mtbio.2026.102874
Weiqing Fang , Jing Zhao , Li Li , Yu Wang , Zhi Ping Xu , Lingxiao Zhang
β-amyloid (Aβ) inhibition significantly attenuates the early-stage Alzheimer's disease (AD) progression, but the improvement in cognitive function remains limited by neuroinflammation. Here, we developed a bioinspired neuroenhancer that concurrently targets both Aβ aggregation and neuroinflammation. Rutin and small interfering RNA targeting beta-site amyloid precursor protein cleaving enzyme 1 (siBACE1) were co-loaded into the calcium phosphate core, which was further coated with lipid bilayers and Angiopep-2/rabies virus glycoprotein 29 peptides to form the multifunctional neuroenhancer (RB@LCP-AR). RB@LCP-AR not only releases siBACE1 to silence BACE1 expression and block Aβ production from the cleavage of amyloid precursor protein, but also releases Rutin to suppress the Aβ aggregation. Moreover, the released Rutin of RB@LCP-AR directly alleviates Aβ-induced mitochondria dysfunction and intracellular ROS production in neuronal cells. Notably, the targeting of RB@LCP-AR to neurons and the inhibition of Aβ reduce the microgliosis and astrogliosis, further alleviating neuroinflammation and synapse loss. Consequently, AD mice receiving RB@LCP-AR treatment efficiently recovered their memory and cognition. Our study thus provides a coordinated targeting of Aβ and neuroinflammation inhibition, holding considerable potential to promote the recovery of memory and cognition in AD.
{"title":"An anti-inflammatory neuroenhancer mitigates amyloid-β pathology to improve Alzheimer's disease therapy","authors":"Weiqing Fang , Jing Zhao , Li Li , Yu Wang , Zhi Ping Xu , Lingxiao Zhang","doi":"10.1016/j.mtbio.2026.102874","DOIUrl":"10.1016/j.mtbio.2026.102874","url":null,"abstract":"<div><div>β-amyloid (Aβ) inhibition significantly attenuates the early-stage Alzheimer's disease (AD) progression, but the improvement in cognitive function remains limited by neuroinflammation. Here, we developed a bioinspired neuroenhancer that concurrently targets both Aβ aggregation and neuroinflammation. Rutin and small interfering RNA targeting beta-site amyloid precursor protein cleaving enzyme 1 (siBACE1) were co-loaded into the calcium phosphate core, which was further coated with lipid bilayers and Angiopep-2/rabies virus glycoprotein 29 peptides to form the multifunctional neuroenhancer (RB@LCP-AR). RB@LCP-AR not only releases siBACE1 to silence BACE1 expression and block Aβ production from the cleavage of amyloid precursor protein, but also releases Rutin to suppress the Aβ aggregation. Moreover, the released Rutin of RB@LCP-AR directly alleviates Aβ-induced mitochondria dysfunction and intracellular ROS production in neuronal cells. Notably, the targeting of RB@LCP-AR to neurons and the inhibition of Aβ reduce the microgliosis and astrogliosis, further alleviating neuroinflammation and synapse loss. Consequently, AD mice receiving RB@LCP-AR treatment efficiently recovered their memory and cognition. Our study thus provides a coordinated targeting of Aβ and neuroinflammation inhibition, holding considerable potential to promote the recovery of memory and cognition in AD.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102874"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170510","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}
Extracellular vesicles (EVs) have emerged as versatile and biocompatible nanocarriers for drug delivery, offering significant advantages over synthetic nanoparticles, which often suffer from rapid clearance, immunogenicity, and limited clinical translation. In this study, we introduce nanoalgosomes, a new class of EVs derived from the marine microalga Tetraselmis chuii, as biogenic carriers for doxorubicin delivery in breast cancer models. Nanoalgosomes exhibit high stability, in vivo biocompatibility, and efficient cargo-loading capacity, making them ideal for therapeutic applications. We optimized doxorubicin-loading strategy, preserving the structural integrity of nanoalgosomes while achieving efficient drug incorporation. Compared to free drug treatments, doxorubicin-loaded nanoalgosomes significantly enhanced drug uptake and its therapeutic effects in breast cancer models. Notably, doxorubicin-loaded nanoalgosomes exhibited a markedly enhanced chemotherapeutic potency compared to free doxorubicin. In 2D tumor cell cultures, nanoalgosomes reduced the doxorubicin the half maximal inhibitory concentration (IC50) by approximately 8-fold. In 3D tumor spheroids, which more closely recapitulate tumor architecture and drug penetration, the IC50 decreased from >2.5 μM for free doxorubicin to 0.7 μM for the doxorubicin-loaded nanoalgosomes, resulting in about 60 % spheroid volume reduction. The superior efficacy of doxorubicin-loaded nanoalgosomes was further validated in vivo in Caenorhabditis elegans, where the IC50 decreased 3-fold for the doxorubicin-loaded nanoalgosomes. These results highlight nanoalgosomes as a sustainable and scalable next-generation drug delivery platform for precision oncology, offering a promising alternative to synthetic nanocarriers.
{"title":"Engineered microalgal extracellular vesicles for efficient doxorubicin delivery and improved therapeutic efficacy in breast cancer","authors":"Giorgia Adamo , Sabrina Picciotto , Pamela Santonicola , Paola Gargano , Estella Rao , Angela Paterna , Samuele Raccosta , Giulia Smeraldi , Carolina Paganini , Daniele P. Romancino , Monica Salamone , Claudio Russo , Paolo Arosio , Elia Di Schiavi , Mauro Manno , Antonella Bongiovanni","doi":"10.1016/j.mtbio.2026.102792","DOIUrl":"10.1016/j.mtbio.2026.102792","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have emerged as versatile and biocompatible nanocarriers for drug delivery, offering significant advantages over synthetic nanoparticles, which often suffer from rapid clearance, immunogenicity, and limited clinical translation. In this study, we introduce nanoalgosomes, a new class of EVs derived from the marine microalga <em>Tetraselmis chuii</em>, as biogenic carriers for doxorubicin delivery in breast cancer models. Nanoalgosomes exhibit high stability, in vivo biocompatibility, and efficient cargo-loading capacity, making them ideal for therapeutic applications. We optimized doxorubicin-loading strategy, preserving the structural integrity of nanoalgosomes while achieving efficient drug incorporation. Compared to free drug treatments, doxorubicin-loaded nanoalgosomes significantly enhanced drug uptake and its therapeutic effects in breast cancer models. Notably, doxorubicin-loaded nanoalgosomes exhibited a markedly enhanced chemotherapeutic potency compared to free doxorubicin. In 2D tumor cell cultures, nanoalgosomes reduced the doxorubicin the half maximal inhibitory concentration (IC<sub>50</sub>) by approximately 8-fold. In 3D tumor spheroids, which more closely recapitulate tumor architecture and drug penetration, the IC<sub>50</sub> decreased from >2.5 μM for free doxorubicin to 0.7 μM for the doxorubicin-loaded nanoalgosomes, resulting in about 60 % spheroid volume reduction. The superior efficacy of doxorubicin-loaded nanoalgosomes was further validated in vivo in <em>Caenorhabditis elegans</em>, where the IC<sub>50</sub> decreased 3-fold for the doxorubicin-loaded nanoalgosomes. These results highlight nanoalgosomes as a sustainable and scalable next-generation drug delivery platform for precision oncology, offering a promising alternative to synthetic nanocarriers.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102792"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079628","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}
Pub Date : 2026-04-01Epub Date: 2026-01-17DOI: 10.1016/j.mtbio.2026.102819
Lihang Qu , Tu Lu , Jun Tan , Xinzhao Chen , Tian Tian , Shixiang Liu , Yajun Gong , Zhihao Jiang , Zhonggui He , Peng Sun , Jin Sun , Xiaoli Ma , Ruidong Gu
Choroidoretinopathy is a major public health concern that causes significant vision impairment. Although therapeutic antibodies have demonstrated potential in treating these conditions, intravitreal injections remain invasive, associated with adverse effects, and require repeated traumatic administrations. Non-invasive drug delivery methods, such as eye drops, represent an ideal alternative but are limited by ocular barriers, making it difficult for drugs to effectively reach specific lesions. In this study, we introduce a novel reactive oxygen species (ROS)-responsive transmembrane peptide–antibody conjugate (PAC) designed for non-invasive, precise antibody delivery to the deep fundus region. The responsive PAC, termed trans-activator of transcription–polyethylene glycol–maleimide (TAT-MPEG)-antibody, is synthesized by linking transmembrane peptides TAT to maleimide via ROS-sensitive diselenide bonds, enabling efficient antibody conjugation. Following eye drop administration, TAT enhances ocular penetration, allowing the conjugate to traverse ocular barriers and deliver antibodies directly to the posterior segment. Moreover, the diselenide bonds facilitate antibody release in oxidative environments, ensuring targeted drug localization at disease sites. In mouse models of choroidal neovascularization and choroidal melanoma, this conjugate demonstrated significant therapeutic efficacy, highlighting its broad clinical potential for the treatment of choroidoretinopathy.
{"title":"ROS-responsive transmembrane peptide-antibody conjugate eyedrops for the non-invasive treatment of choroidoretinopathy","authors":"Lihang Qu , Tu Lu , Jun Tan , Xinzhao Chen , Tian Tian , Shixiang Liu , Yajun Gong , Zhihao Jiang , Zhonggui He , Peng Sun , Jin Sun , Xiaoli Ma , Ruidong Gu","doi":"10.1016/j.mtbio.2026.102819","DOIUrl":"10.1016/j.mtbio.2026.102819","url":null,"abstract":"<div><div>Choroidoretinopathy is a major public health concern that causes significant vision impairment. Although therapeutic antibodies have demonstrated potential in treating these conditions, intravitreal injections remain invasive, associated with adverse effects, and require repeated traumatic administrations. Non-invasive drug delivery methods, such as eye drops, represent an ideal alternative but are limited by ocular barriers, making it difficult for drugs to effectively reach specific lesions. In this study, we introduce a novel reactive oxygen species (ROS)-responsive transmembrane peptide–antibody conjugate (PAC) designed for non-invasive, precise antibody delivery to the deep fundus region. The responsive PAC, termed trans-activator of transcription–polyethylene glycol–maleimide (TAT-MPEG)-antibody, is synthesized by linking transmembrane peptides TAT to maleimide via ROS-sensitive diselenide bonds, enabling efficient antibody conjugation. Following eye drop administration, TAT enhances ocular penetration, allowing the conjugate to traverse ocular barriers and deliver antibodies directly to the posterior segment. Moreover, the diselenide bonds facilitate antibody release in oxidative environments, ensuring targeted drug localization at disease sites. In mouse models of choroidal neovascularization and choroidal melanoma, this conjugate demonstrated significant therapeutic efficacy, highlighting its broad clinical potential for the treatment of choroidoretinopathy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102819"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079674","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}
Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.mtbio.2026.102824
Xi Yu , Yujie He , Jiani Zhong , Yue Li , Yuan Zhu , Yingying Chen , Jingbo Yin , Zeting Yuan , Peihao Yin
Colorectal cancer (CRC) management is significantly hindered by the challenges of early detection and the high rates of recurrence and metastasis following surgery. Systemic postoperative therapies are frequently compromised by adverse effects and drug resistance. To address this, we engineered a localized and combinatorial platform by integrating Bufalin (BU), a potent anti-tumor agent from traditional Chinese medicine, into citric acid-based carbon dots modified with hyaluronic acid (BU-CDsCA-HA), which were subsequently incorporated into a Janus-structured membrane. This design enabled robust adhesion to post-resection tumor sites, ensuring sustained local drug release and spatially confined photothermal/photodynamic therapy (PTT/PDT) while effectively sparing adjacent healthy tissues from thermal damage. Upon near-infrared (NIR) irradiation, the synergistic BU-PTT/PDT action induced potent immunogenic cell death (ICD), as evidenced by the release of damage-associated molecular patterns (DAMPs), thereby initiating a systemic anti-tumor immune response. Concurrently, BU down-regulated heat shock proteins (HSPs) and HIF-1α expression, leading to the suppression of tumor PD-L1 and effectively countering immune escape. In orthotopic and metastatic CRC mouse models, this multifunctional Janus membrane system demonstrated remarkable efficacy in preventing local recurrence and distant metastasis. This outcome was attributed to the concerted effect of immediate cytotoxic ablation and the elicited durable anti-tumor immunity. Our work presents a novel biomaterial-based strategy that enhanced the efficacy and safety of postoperative CRC treatment, offering a versatile platform for site-specific combination therapy.
{"title":"Immediate tumor killing and long-term anti-tumor immunoreaction induced by Bufalin-loaded phototherapeutic Janus membrane in CRC postoperative therapy","authors":"Xi Yu , Yujie He , Jiani Zhong , Yue Li , Yuan Zhu , Yingying Chen , Jingbo Yin , Zeting Yuan , Peihao Yin","doi":"10.1016/j.mtbio.2026.102824","DOIUrl":"10.1016/j.mtbio.2026.102824","url":null,"abstract":"<div><div>Colorectal cancer (CRC) management is significantly hindered by the challenges of early detection and the high rates of recurrence and metastasis following surgery. Systemic postoperative therapies are frequently compromised by adverse effects and drug resistance. To address this, we engineered a localized and combinatorial platform by integrating Bufalin (BU), a potent anti-tumor agent from traditional Chinese medicine, into citric acid-based carbon dots modified with hyaluronic acid (BU-CDs<sub>CA-HA</sub>), which were subsequently incorporated into a Janus-structured membrane. This design enabled robust adhesion to post-resection tumor sites, ensuring sustained local drug release and spatially confined photothermal/photodynamic therapy (PTT/PDT) while effectively sparing adjacent healthy tissues from thermal damage. Upon near-infrared (NIR) irradiation, the synergistic BU-PTT/PDT action induced potent immunogenic cell death (ICD), as evidenced by the release of damage-associated molecular patterns (DAMPs), thereby initiating a systemic anti-tumor immune response. Concurrently, BU down-regulated heat shock proteins (HSPs) and HIF-1α expression, leading to the suppression of tumor PD-L1 and effectively countering immune escape. In orthotopic and metastatic CRC mouse models, this multifunctional Janus membrane system demonstrated remarkable efficacy in preventing local recurrence and distant metastasis. This outcome was attributed to the concerted effect of immediate cytotoxic ablation and the elicited durable anti-tumor immunity. Our work presents a novel biomaterial-based strategy that enhanced the efficacy and safety of postoperative CRC treatment, offering a versatile platform for site-specific combination therapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102824"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079676","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}
Pub Date : 2026-04-01Epub Date: 2026-01-10DOI: 10.1016/j.mtbio.2026.102781
Jing Li , Mengyuan Hou , Run Wang , Meng Li , Junying Chen , Minxuan Ge , Yachen Fei , Xianling Gao , Chengdong Zhang , Jin Zhong , Shuangying Gui , Mengjie Li , Jinghua Hao , Jian Guo
Periodontitis is a chronic oral disease characterized by gingival inflammation and periodontium injury due to repeated pathogenic bacteria infection and overactive inflammatory response. Multidrug resistance and the quick loss of antibiotics in the oral cavity create challenges for treatment. Therefore, a novel non-antibiotic-dependent pharmaceutical strategy is crucial for clinical treatment of periodontitis. In this study, we developed a lipid complex-in-thermogel delivery system (IQ-ML@Gel) co-loading the photosensitizer of indocyanine green and the immunomodulator of quercetin. IQ-ML@Gel could stably adhere in the periodontal pocket through liquid-solid transformation in situ. In vitro studies confirmed the efficient elimination of Porphyromonas gingivalis and Fusobacterium nucleatum by multimodal photothermal/photodynamic effects. Notably, IQ-ML displayed rapid macrophage uptake and an immunomodulatory effect through M1-M2 phenotypic polarization. In in vivo periodontitis treatment, IQ-ML@Gel effectively reverses the inflammatory microenvironment to promote periodontal tissue repair, including stimulating the regeneration of gingival collagen and alveolar bone. Overall, IQ-ML@Gel provides a promising non-antibiotic lipid complex-in-thermogel platform for periodontitis treatment.
{"title":"Non-antibiotic lipid complex-in-thermogel strikes twice: multimodal photosensitive antibacterial meets immunomodulation-boosted healing for periodontitis treatment","authors":"Jing Li , Mengyuan Hou , Run Wang , Meng Li , Junying Chen , Minxuan Ge , Yachen Fei , Xianling Gao , Chengdong Zhang , Jin Zhong , Shuangying Gui , Mengjie Li , Jinghua Hao , Jian Guo","doi":"10.1016/j.mtbio.2026.102781","DOIUrl":"10.1016/j.mtbio.2026.102781","url":null,"abstract":"<div><div>Periodontitis is a chronic oral disease characterized by gingival inflammation and periodontium injury due to repeated pathogenic bacteria infection and overactive inflammatory response. Multidrug resistance and the quick loss of antibiotics in the oral cavity create challenges for treatment. Therefore, a novel non-antibiotic-dependent pharmaceutical strategy is crucial for clinical treatment of periodontitis. In this study, we developed a lipid complex-in-thermogel delivery system (IQ-ML@Gel) co-loading the photosensitizer of indocyanine green and the immunomodulator of quercetin. IQ-ML@Gel could stably adhere in the periodontal pocket through liquid-solid transformation <em>in situ</em>. <em>In vitro</em> studies confirmed the efficient elimination of <em>Porphyromonas gingivalis</em> and <em>Fusobacterium nucleatum</em> by multimodal photothermal/photodynamic effects. Notably, IQ-ML displayed rapid macrophage uptake and an immunomodulatory effect through M1-M2 phenotypic polarization. In <em>in vivo</em> periodontitis treatment, IQ-ML@Gel effectively reverses the inflammatory microenvironment to promote periodontal tissue repair, including stimulating the regeneration of gingival collagen and alveolar bone. Overall, IQ-ML@Gel provides a promising non-antibiotic lipid complex-in-thermogel platform for periodontitis treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102781"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981388","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}
Pub Date : 2026-04-01Epub Date: 2026-01-16DOI: 10.1016/j.mtbio.2026.102814
Yunhao Zhai , Xiangheng Guan , Caorui Lu , Ruixuan Sun , Yun Qian , Yi Li , Kaihang Zhang , Xu Wang , Linbin Xu , Xinghao Yin , Shang Guo , Jinglei Wu , Cunyi Fan
Non-transecting peripheral nerve injuries require effective inflammation control, support of axon regeneration, and strategies that minimize additional surgical trauma. Injectable hydrogels are attractive carriers for local therapy, and chitosan is a widely used biocompatible matrix; however, conventional chitosan systems often depend on acidic dissolution and crosslinking or cytotoxic crosslinkers, which may aggravate nerve injury and hinder clinical translation. Here, we develop an injectable chitosan-based hydrogel (IBU-CS-GP) in which ibuprofen is complexed with chitosan for solubility range expansion toward near-neutral pH, thereby permitting genipin-mediated crosslinking under near-physiological pH and resolving the mismatch between chitosan solubility and the optimal pH for genipin. The resulting hydrogel forms a stable depot after perineural injection, enabling minimally invasive in situ gelation and localized drug delivery. We characterize its physicochemical properties, ibuprofen release profile, and biosafety, and evaluate its immunomodulatory and pro-regenerative effects in vitro and in a rat sciatic nerve crush model. In vitro, the IBU-CS-GP hydrogel suppresses macrophage inflammatory activation and reduces pro-inflammatory mediator production, thereby promoting a repair-supportive phenotype; in parallel, it indirectly enhances endothelial and stromal cell activities involved in angiogenesis and matrix remodeling. In vivo, perineural injection results in sustained ibuprofen release, accompanied by accelerated recovery of gait and nerve conduction, better preservation of gastrocnemius muscle mass and architecture, and more organized axon regeneration. These data suggest that the IBU-CS-GP hydrogel is a promising minimally invasive local therapy for non-transecting peripheral nerve injuries, as it enables near-neutral-pH in situ gelation and modulates the post-injury microenvironment.
{"title":"Injectable chitosan-based hydrogel via in situ gelation modulates the inflammatory microenvironment and facilitates minimally invasive repair of peripheral nerve injury","authors":"Yunhao Zhai , Xiangheng Guan , Caorui Lu , Ruixuan Sun , Yun Qian , Yi Li , Kaihang Zhang , Xu Wang , Linbin Xu , Xinghao Yin , Shang Guo , Jinglei Wu , Cunyi Fan","doi":"10.1016/j.mtbio.2026.102814","DOIUrl":"10.1016/j.mtbio.2026.102814","url":null,"abstract":"<div><div>Non-transecting peripheral nerve injuries require effective inflammation control, support of axon regeneration, and strategies that minimize additional surgical trauma. Injectable hydrogels are attractive carriers for local therapy, and chitosan is a widely used biocompatible matrix; however, conventional chitosan systems often depend on acidic dissolution and crosslinking or cytotoxic crosslinkers, which may aggravate nerve injury and hinder clinical translation. Here, we develop an injectable chitosan-based hydrogel (IBU-CS-GP) in which ibuprofen is complexed with chitosan for solubility range expansion toward near-neutral pH, thereby permitting genipin-mediated crosslinking under near-physiological pH and resolving the mismatch between chitosan solubility and the optimal pH for genipin. The resulting hydrogel forms a stable depot after perineural injection, enabling minimally invasive in situ gelation and localized drug delivery. We characterize its physicochemical properties, ibuprofen release profile, and biosafety, and evaluate its immunomodulatory and pro-regenerative effects in vitro and in a rat sciatic nerve crush model. In vitro, the IBU-CS-GP hydrogel suppresses macrophage inflammatory activation and reduces pro-inflammatory mediator production, thereby promoting a repair-supportive phenotype; in parallel, it indirectly enhances endothelial and stromal cell activities involved in angiogenesis and matrix remodeling. In vivo, perineural injection results in sustained ibuprofen release, accompanied by accelerated recovery of gait and nerve conduction, better preservation of gastrocnemius muscle mass and architecture, and more organized axon regeneration. These data suggest that the IBU-CS-GP hydrogel is a promising minimally invasive local therapy for non-transecting peripheral nerve injuries, as it enables near-neutral-pH in situ gelation and modulates the post-injury microenvironment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102814"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024481","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}
Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.mtbio.2026.102830
Shaopeng Zhang , Shaokang Yang , Mingqi Li , Hao Zhang , Yue Cao , Shiqi Bai , Wei Li , Bin Wang , Donghao Qu , Ziqian Wang , Wanying Li , Yanxu Sun , Daguang Wang , Yinghui Wang , Hongjie Zhang
Despite the immunotherapy has achieved the progress for advanced colorectal cancer, the unsatisfactory treatment effect remains a challenge due to the deficient immune response. In this work, we constructed a tumor microenvironments (TME)-responsive biodegradable cuproptosis inducer (ZnO2-Cu@HA, ZCH) through cation-exchange method for amplifying the immune response. Compared to free copper ions, ZCH cloud achieve the controllable release of Cu2+ in tumor site, trggering efficient cuproptosis but reducing the side effect of normal tissues. Furthermore, the released Zn2+ could also inhibit intracellular glycolysis and ATP generation, then block the ATP7B to reduce the efflux of copper ions. Meanwhile, ZCH broke intracellular redox homeostasis via the release of exogenous H2O2, Cu+-mediated Fenton-like reaction and Zn2+-induced endogenous mitoROS, amplifying the cuproptosis to inducing immunogenic cell death (ICD) triggered for highly efficient immunotherapy of colorectal cancer. These findings demonstrated that it is a promising strategy of inducing efficient cuproptosis by the synergistic effect of accumulation of copper ions, inhibiting glycolysis and down-regulation GSH for efficient immunotherapy of colorectal cancer.
{"title":"Copper-enriched zinc peroxides induced cuproptosis through concurrent metabolic and oxidative dysregulation for boosting immunotherapy in colorectal cancer","authors":"Shaopeng Zhang , Shaokang Yang , Mingqi Li , Hao Zhang , Yue Cao , Shiqi Bai , Wei Li , Bin Wang , Donghao Qu , Ziqian Wang , Wanying Li , Yanxu Sun , Daguang Wang , Yinghui Wang , Hongjie Zhang","doi":"10.1016/j.mtbio.2026.102830","DOIUrl":"10.1016/j.mtbio.2026.102830","url":null,"abstract":"<div><div>Despite the immunotherapy has achieved the progress for advanced colorectal cancer, the unsatisfactory treatment effect remains a challenge due to the deficient immune response. In this work, we constructed a tumor microenvironments (TME)-responsive biodegradable cuproptosis inducer (ZnO<sub>2</sub>-Cu@HA, ZCH) through cation-exchange method for amplifying the immune response. Compared to free copper ions, ZCH cloud achieve the controllable release of Cu<sup>2+</sup> in tumor site, trggering efficient cuproptosis but reducing the side effect of normal tissues. Furthermore, the released Zn<sup>2+</sup> could also inhibit intracellular glycolysis and ATP generation, then block the ATP7B to reduce the efflux of copper ions. Meanwhile, ZCH broke intracellular redox homeostasis via the release of exogenous H<sub>2</sub>O<sub>2</sub>, Cu<sup>+</sup>-mediated Fenton-like reaction and Zn<sup>2+</sup>-induced endogenous mitoROS, amplifying the cuproptosis to inducing immunogenic cell death (ICD) triggered for highly efficient immunotherapy of colorectal cancer. These findings demonstrated that it is a promising strategy of inducing efficient cuproptosis by the synergistic effect of accumulation of copper ions, inhibiting glycolysis and down-regulation GSH for efficient immunotherapy of colorectal cancer.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102830"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024395","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}
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