Advanced Healthcare Materials最新文献_第8页

An Expandable Brain-Machine Interface Enabled by Origami Materials and Structures for Tracking Epileptic Traveling Waves.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-20 DOI: 10.1002/adhm.202404947

Tiancheng Sheng, Jingwei Li, Lingyi Zheng, Nianzhen Du, Mingxiao Xie, Xiaolong Wang, Xize Gao, Mengsha Huang, Shenghan Wen, Wenqian Liu, Yong Guo, Yi Yao, Xiaoqiu Shao, Lianqing Liu, Jing Xu, Yilong Wang, Mingjun Zhang

引用次数: 0

Functionalized Cerium Oxide Nanoparticles Enhance Penetration into Melanoma Spheroids In Vivo through Angiogenesis.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-20 DOI: 10.1002/adhm.202405129

Lu Fu, Joel M Yong, Robyn Yeh, Florence Bartlett, John M Whitelock, Megan S Lord

{"title":"Functionalized Cerium Oxide Nanoparticles Enhance Penetration into Melanoma Spheroids In Vivo through Angiogenesis.","authors":"Lu Fu, Joel M Yong, Robyn Yeh, Florence Bartlett, John M Whitelock, Megan S Lord","doi":"10.1002/adhm.202405129","DOIUrl":"https://doi.org/10.1002/adhm.202405129","url":null,"abstract":"Angiogenesis is a crucial step in tumor progression, including melanoma, making anti-angiogenic strategies a widely explored treatment approach. However, both innate and acquired resistance to these therapies suggest that this approach may need re-evaluation. Nanoparticles have gained attention for their potential to enhance drug delivery and retention within tumors via the bloodstream. However, the in vitro screening of nanoparticles is limited by the inability of preclinical models to replicate the complex tumor microenvironment, especially the blood supply. Here, it is demonstrated that melanoma cells embedded in Matrigel spheroids can engraft in and be vascularized by the chorioallantoic membrane (CAM) of fertilized chicken eggs. This model allows for the assessment of nanoparticle toxicity and accumulation in tumor spheroids, as well as functional effects such as angiogenesis. Cerium oxide nanoparticles (nanoceria) and their surface functionalized derivatives are widely explored for biomedical applications due to their ability to modulate oxidative stress and angiogenesis. Here, it is observed that heparin functionalized nanoceria penetrate melanoma spheroids in the CAM and promote spheroid vascularization to a greater extent than nanoceria alone. This study aids in the development of preclinical cancer models for nanoparticle screening and provides new insight into the interplay between nanoparticle surface coatings and biological effects.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2405129"},"PeriodicalIF":10.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intrinsically Pro-Apoptotic Gold Nanoclusters for Optical Tracing and Inhibition of Solid Tumors.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-20 DOI: 10.1002/adhm.202405005

Priyanka Sharma, Hao Yuan, Ruchi Verma, Nisha Mehla, Hemant Hemant, Poonam Sagar, Clothilde Comby-Zerbino, Isabelle Russier-Antoine, Christophe Moulin, Pierre-François Brevet, Nitin Singhal, Prakash P Neelakandan, Sonalika Vaidya, Changkui Fu, Md Ehesan Ali, Rohit Srivastava, Andrew Whittaker, Rodolphe Antoine, Asifkhan Shanavas

{"title":"Intrinsically Pro-Apoptotic Gold Nanoclusters for Optical Tracing and Inhibition of Solid Tumors.","authors":"Priyanka Sharma, Hao Yuan, Ruchi Verma, Nisha Mehla, Hemant Hemant, Poonam Sagar, Clothilde Comby-Zerbino, Isabelle Russier-Antoine, Christophe Moulin, Pierre-François Brevet, Nitin Singhal, Prakash P Neelakandan, Sonalika Vaidya, Changkui Fu, Md Ehesan Ali, Rohit Srivastava, Andrew Whittaker, Rodolphe Antoine, Asifkhan Shanavas","doi":"10.1002/adhm.202405005","DOIUrl":"https://doi.org/10.1002/adhm.202405005","url":null,"abstract":"Intrinsically theranostic metal nanoclusters are rare unless the stabilizing ligands exhibit therapeutic properties. A promising class of quasi-molecular, near-infrared (NIR) emitting, cytotoxic gold nanoclusters, coined as AXE (Au eXcitable and Eliminable) stabilized through terminal thioester groups on fluorinated, and crosslinked polymers, is presented for simultaneous bioimaging & therapy. Nano Variable Temperature-Electrospray ionization mass spectrometry analysis of these aqueous stable nanoclusters revealed 5 to 7 core gold atoms, with SAXS measurement confirming average size to be under 1 nm, consistent with the theoretical maximum for few atom planar gold clusters. Despite its small size, AXE exhibits a remarkable Stoke shift of ≈470 nm and emission range spanning 700 to 1100 nm. Fluorination notably enhanced the quantum yield by up to twofold, attributed to charge transfer from the fluorinated monomer to the gold core, as indicated by Löwdin charge distribution analysis. The AXE nanocluster demonstrated dose-dependent pro-apoptotic effects on cancer cells while sparing normal cells at lower concentrations. Preclinical evaluation in a breast tumor model confirmed its anticancer efficacy, with intravenous and intraperitoneal administrations significantly inhibiting tumor growth and controlling lung metastasis, surpassing the clinical standard, doxorubicin.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2405005"},"PeriodicalIF":10.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered Hollow Nanocomplex Combining Photothermal and Antioxidant Strategies for Targeted Tregs Depletion and Potent Immune Activation in Tumor Immunotherapy.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-20 DOI: 10.1002/adhm.202405124

Qi Sun, Yuyan Wang, Hetian Ren, Shiyuan Hou, Kaiyi Niu, Liu Wang, Siyu Liu, Jingyi Ye, Chunying Cui, Xianrong Qi

{"title":"Engineered Hollow Nanocomplex Combining Photothermal and Antioxidant Strategies for Targeted Tregs Depletion and Potent Immune Activation in Tumor Immunotherapy.","authors":"Qi Sun, Yuyan Wang, Hetian Ren, Shiyuan Hou, Kaiyi Niu, Liu Wang, Siyu Liu, Jingyi Ye, Chunying Cui, Xianrong Qi","doi":"10.1002/adhm.202405124","DOIUrl":"https://doi.org/10.1002/adhm.202405124","url":null,"abstract":"In the tumor immunosuppressive microenvironment (TIME), regulatory T cells (Tregs) critically suppress anticancer immunity, characterized by high expression of glucocorticoid-induced TNF receptor (GITR) expression and sensitivity to reactive oxygen species (ROS). This study develops a near-infrared (NIR)-responsive hollow nanocomplex (HPDA-OPC/DTA-1) using hollow polydopamine nanoparticles (HPDA), endowed with thermogenic and antioxidative properties, specifically targeting Tregs to activate antitumor immunity. The GITR agonist DTA-1, combined with the antioxidant oligomeric proanthocyanidins (OPC) to deplete Tregs. However, Tregs depletion alone may not sufficiently trigger robust immune responses. The HPDA nanocarrier enhances thermogenic and antioxidative capacities, supporting photothermal immunotherapy. The HPDA-OPC/DTA-1 demonstrates NIR responsiveness for both photothermal therapy (PTT) and OPC release, while facilitating Tregs depletion via DTA-1 and reducing ROS levels, thereby reviving antitumor immunity. Notably, intratumoral CD4+CD25+FOXP3+ Tregs exhibited a 4.08-fold reduction alongside a 49.11-fold increase in CD8+ T cells/Tregs relative to controls. Enhanced dendritic cells (DCs) maturation and immunogenic cell death (ICD) induction further demonstrate that HPDA-OPC/DTA-1 alleviates immunosuppression and activates antitumor immunity. Ultimately, the observed tumor inhibitory effect (tumor volume: 6.75-fold versus the control) and an over 80% survival rate highlight the therapeutic potential of combining Tregs targeting, antioxidant strategy, and photothermal immunotherapy for effective cancer treatment.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2405124"},"PeriodicalIF":10.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel pH-Responsive Baicalein@Chitosan Hydrogel for the Topical Treatment of Herpes Simplex Virus Type 1 Skin Infections: Therapeutic Potential and Mechanisms.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-20 DOI: 10.1002/adhm.202403961

Yuhui Lu, Liying Zhou, Alu Ouyang, Xin Wang, Xiaoyang Wei, Shangping Xing, Feifei Nong, Jinquan Lin, Haotong Wang, Yuan Li, Jie Deng, Yilu Bao, Jie Yang, Ronghua Jin, Zhuo Luo

{"title":"A Novel pH-Responsive Baicalein@Chitosan Hydrogel for the Topical Treatment of Herpes Simplex Virus Type 1 Skin Infections: Therapeutic Potential and Mechanisms.","authors":"Yuhui Lu, Liying Zhou, Alu Ouyang, Xin Wang, Xiaoyang Wei, Shangping Xing, Feifei Nong, Jinquan Lin, Haotong Wang, Yuan Li, Jie Deng, Yilu Bao, Jie Yang, Ronghua Jin, Zhuo Luo","doi":"10.1002/adhm.202403961","DOIUrl":"https://doi.org/10.1002/adhm.202403961","url":null,"abstract":"Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen primarily transmitted through skin-to-skin contact. Traditional antiviral drugs like acyclovir (ACV) have limitations due to viral resistance and side effects, necessitating the development of alternative therapeutic strategies. Drug-loaded hydrogels have emerged as a promising approach for managing various skin infections. Considering the low-pH microenvironment following HSV-1 infection, a pH-responsive baicalein@chitosan (B@C) hydrogel is developed for the topical treatment of HSV-1 skin infections. This hydrogel is synthesized by incorporating baicalein, a natural flavonoid, into a chitosan matrix modified with 4-formylphenylboronic acid and protocatechualdehyde to achieve potent anti-HSV-1 activity and pH-responsiveness. In vitro results demonstrated the hydrogel's pH-dependent inhibitory effect on HSV-1 infections, including ACV-resistant strains. Subsequent investigations confirmed its efficacy in multiple murine infection models. Mechanistically, the B@C hydrogel inhibited viral replication by modulating the phosphorylation of inhibitor of nuclear factor kappa-B kinase subunit beta, promoted collagen synthesis, and decreased reactive oxygen species generation. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis revealed a sustained release of baicalein from the hydrogel, ensuring long-term drug retention in HSV-1-infected skin tissues. Collectively, these findings suggest that the B@C hydrogel holds significant potential for the therapeutic management of HSV-1 skin infections.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403961"},"PeriodicalIF":10.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Programable Prodrug Nanomodulator Targets Tumor Redox Homeostasis Imbalance to Amplify Disulfidptosis and Immunogenic Pyroptosis for Breast Tumor Immunotherapy.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-20 DOI: 10.1002/adhm.202500272

Ayeskanta Mohanty, Adityanarayan Mohapatra, Woojin Yang, Seunghyun Choi, Aravindkumar Sundaram, Yong-Yeon Jeong, Chang-Moon Lee, Jiwon Seo, In-Kyu Park

{"title":"Programable Prodrug Nanomodulator Targets Tumor Redox Homeostasis Imbalance to Amplify Disulfidptosis and Immunogenic Pyroptosis for Breast Tumor Immunotherapy.","authors":"Ayeskanta Mohanty, Adityanarayan Mohapatra, Woojin Yang, Seunghyun Choi, Aravindkumar Sundaram, Yong-Yeon Jeong, Chang-Moon Lee, Jiwon Seo, In-Kyu Park","doi":"10.1002/adhm.202500272","DOIUrl":"https://doi.org/10.1002/adhm.202500272","url":null,"abstract":"Despite the great potential of photodynamic therapy (PDT), its success remains compromised by the abnormal redox homeostasis of tumor cells, which supports survival, growth, and resistance to oxidative therapeutic interventions by neutralizing reactive oxygen species (ROS). To overcome this barrier, a multifunctional prodrug nanomodulator (Pro@FLNC) is designed to induce disulfidptosis and immunogenic pyroptosis to trigger an antitumor immune response. Pro@FLNC features a prodrug core-shell structure where ursolic acid (UA) and Chlorin e6 (Ce6) are conjugated via a GSH-responsive linker and encapsulated in a DSPE-PEG-FA lipid shell for enhanced stability, biocompatibility, and tumor-specific targeting. Within the tumor microenvironment (TME), Pro@FLNC depletes intracellular GSH, disrupts redox homeostasis, and releases Ce6 and UA, triggering oxidative stress and mitochondrial dysfunction. These mechanisms amplify ROS production, promote lipid peroxidation, and initiate disulfidptosis, evidenced by increased SLC7A11 expression and F-actin collapse. Elevated ROS levels and metabolic imbalance-triggered disulfidptosis further activate immunogenic pyroptosis, releasing damage-associated molecular patterns (DAMPs) that stimulate dendritic cell maturation and cytotoxic T-cell activation. Together, Pro@FLNC reshapes the TME, reduces immunosuppressive cells, and promotes CD8+ T-cell infiltration, effectively suppressing primary tumors and metastases. This programmed prodrug nanomodulator offers a promising strategy to enhance PDT and immunotherapy for advanced breast cancer.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500272"},"PeriodicalIF":10.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Supercritical Fluid-Processed Multifunctional Hybrid Decellularized Extracellular Matrix with Chitosan Hydrogel for Improving Photoaged Dermis Microenvironment.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-20 DOI: 10.1002/adhm.202403213

Seol-Ha Jeong, Jae Jun Kang, Ki-Myo Kim, Mi Hyun Lee, Misun Cha, Su Hee Kim, Ji-Ung Park

{"title":"Supercritical Fluid-Processed Multifunctional Hybrid Decellularized Extracellular Matrix with Chitosan Hydrogel for Improving Photoaged Dermis Microenvironment.","authors":"Seol-Ha Jeong, Jae Jun Kang, Ki-Myo Kim, Mi Hyun Lee, Misun Cha, Su Hee Kim, Ji-Ung Park","doi":"10.1002/adhm.202403213","DOIUrl":"https://doi.org/10.1002/adhm.202403213","url":null,"abstract":"To address the demand for reconstructive procedures in extensive subcutaneous tissue defects and significant dermis matrix loss, vascularized adipose tissue regeneration is essential for maintaining volume after material degradation. Accordingly, a double-crosslinked hydrogel that combines polyethylene glycol (PEG)-crosslinked carboxymethyl chitosan (CMC) with a hybrid decellularized extracellular matrix (dECM) is developed. The dECM, sourced from porcine adipose and cardiac tissues, processed using a supercritical fluid technique (scCO2-EtOH) retains 1.5-5-fold more angiogenic and adipogenic cytokines than that processed using traditional methods. This hybrid dECM-based filler demonstrates excellent physical properties and injectability, with injection forces being significantly less than that for crosslinked hyaluronic acid (HA) fillers. Upon incubation at 37 °C, the storage modulus of the fillers increases substantially, eventually enhancing their moldability from additional crosslinking and the thermosensitive nature of collagen. Assessments in a UVB-induced photoaging mouse model indicate that the material maintains superior shape stability, durability, and supports vascularized tissue regeneration, reduces inflammation, and enhances VEGF expression and ECM maturation more effectively compared with that using other fillers. These promising results suggest that the material can serve as a highly effective multifunctional solution for injectable regenerative medical applications and is well-suited for potential clinical trials.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403213"},"PeriodicalIF":10.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel 3D High-Throughput Phenotypic Drug Screening Pipeline to Identify Drugs with Repurposing Potential for the Treatment of Ovarian Cancer.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-20 DOI: 10.1002/adhm.202404117

Nazanin Karimnia, Amy L Wilson, Brittany R Doran, Jennie Do, Amelia Matthews, Gwo Y Ho, Magdalena Plebanski, Thomas W Jobling, Andrew N Stephens, Maree Bilandzic

{"title":"A Novel 3D High-Throughput Phenotypic Drug Screening Pipeline to Identify Drugs with Repurposing Potential for the Treatment of Ovarian Cancer.","authors":"Nazanin Karimnia, Amy L Wilson, Brittany R Doran, Jennie Do, Amelia Matthews, Gwo Y Ho, Magdalena Plebanski, Thomas W Jobling, Andrew N Stephens, Maree Bilandzic","doi":"10.1002/adhm.202404117","DOIUrl":"https://doi.org/10.1002/adhm.202404117","url":null,"abstract":"Ovarian cancer (OC) poses a significant clinical challenge due to its high recurrence rates and resistance to standard therapies, particularly in advanced stages where recurrence is common, and treatment is predominantly palliative. Personalized treatments, while effective in other cancers, remain underutilized in OC due to a lack of reliable biomarkers predicting clinical outcomes. Accordingly, precision medicine approaches are limited, with PARP inhibitors showing efficacy only in specific genetic contexts. Drug repurposing offers a promising, rapidly translatable strategy by leveraging existing pharmacological data to identify new treatments for OC. Patient-derived polyclonal spheroids, isolated from ascites fluid closely mimic the clinical behavior of OC, providing a valuable model for drug testing. Using these spheroids, a high-throughput drug screening pipeline capable of evaluating both cytotoxicity and anti-migratory properties of a diverse drug library, including FDA-approved, investigational, and newly approved compounds is developed. The findings highlight the importance of 3D culture systems, revealing a poor correlation between drug efficacy in traditional 2D models and more clinically relevant 3D spheroids. This approach has expedited the identification of promising candidates, such as rapamycin, which demonstrated limited activity as a monotherapy but synergized effectively with standard treatments like cisplatin and paclitaxel in vitro. In combination with platinum-based therapy, Rapamycin led to significant in vitro cytotoxicity and a marked reduction in tumor burden in a syngeneic in vivo model. This proof-of-concept study underscores the potential of drug repurposing to rapidly advance new treatments into clinical trials for OC, offering renewed hope for patients with advanced disease.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404117"},"PeriodicalIF":10.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced cGAS-STING Activation and Immune Response by LPDAM Platform-Based Lapachone-Chemical-Photothermal Synergistic Therapy for Colorectal Cancer.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-19 DOI: 10.1002/adhm.202403309

Xiaoyu Pan, Yan Lin, Chunlin Lin, Songyi Liu, Penghang Lin, Xiang Lin, Ruofan He, ZiChen Ye, Jianxin Ye, Guangwei Zhu

{"title":"Enhanced cGAS-STING Activation and Immune Response by LPDAM Platform-Based Lapachone-Chemical-Photothermal Synergistic Therapy for Colorectal Cancer.","authors":"Xiaoyu Pan, Yan Lin, Chunlin Lin, Songyi Liu, Penghang Lin, Xiang Lin, Ruofan He, ZiChen Ye, Jianxin Ye, Guangwei Zhu","doi":"10.1002/adhm.202403309","DOIUrl":"https://doi.org/10.1002/adhm.202403309","url":null,"abstract":"The cGAS-STING signaling pathway is a pivotal immune response mechanism that bridges tumor and immune cell interactions. This study describes a multifunctional LPDAM nanoplatform integrating Lapachone, polydopamine (PDA), and Mn2+, which synergistically kills tumor cells and activates the cGAS-STING pathway, thereby inducing DC maturation and T cell activation to achieve potent antitumor immunity. In the tumor microenvironment, Lapachone generates H2O2 via the NAD(P)H:quinone oxidoreductase 1 (NQO1 enzyme), while Mn2+ catalyze H2O2 conversion into •OH through chemodynamic effects (CDT). The photothermal effects (PTT) of PDA further amplify this cascade reaction, producing reactive oxygen species (ROS) that damage tumor mitochondria and release mitochondrial DNA (mtDNA). The released mtDNA activates the cGAS-STING pathway, while Mn2+ enhances the sensitivity of cGAS to mtDNA, leading to robust antitumor immunity. Concurrently, photothermal-induced immunogenic cell death (ICD) promotes dendritic cells (DCs) maturation, further strengthening immune responses. Moreover, Mn2⁺ also serves as a contrast agent for T1-weighted magnetic resonance imaging (MRI), offering precise tumor visualization. This study demonstrates that the LPDAM nanoplatform facilitates Lapachone/CDT/PTT synergistic therapy under MRI guidance, showcasing its potential as an innovative strategy for combined immunotherapy in clinical oncology.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403309"},"PeriodicalIF":10.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tailoring Lipid Nanoparticle with Ex Situ Incorporated Conjugated Oligoelectrolyte for Enhanced mRNA Delivery Efficiency.

IF 1 2区医学

Advanced Healthcare Materials Pub Date : 2025-03-19 DOI: 10.1002/adhm.202405048

Wilson Wee Mia Soh, Esteban Finol, Samuel J W Chan, Ji-Yu Zhu, Sebastian Sean Jing Kang Liau, Ava Bier, Eng Eong Ooi, Guillermo C Bazan

{"title":"Tailoring Lipid Nanoparticle with Ex Situ Incorporated Conjugated Oligoelectrolyte for Enhanced mRNA Delivery Efficiency.","authors":"Wilson Wee Mia Soh, Esteban Finol, Samuel J W Chan, Ji-Yu Zhu, Sebastian Sean Jing Kang Liau, Ava Bier, Eng Eong Ooi, Guillermo C Bazan","doi":"10.1002/adhm.202405048","DOIUrl":"https://doi.org/10.1002/adhm.202405048","url":null,"abstract":"Developing new lipid nanoparticle (LNP) formulations typically involves reconstruction from separate elements followed by rigorous purification steps, contributing to drawn-out drug discovery processes. Membrane-intercalating conjugated oligoelectrolytes (COEs) are water-soluble molecules featuring a conjugated backbone and peripheral ionic groups, specifically designed to spontaneously integrate into lipid bilayers. Herein, an ex situ strategy to \"dope\" the representative COE-S6 into pre-formed messenger RNA-LNPs (mRNA-LNPs) is presented, exploiting its spontaneous membrane intercalation property through a straightforward add-and-mix procedure. Incorporating 0.2% COE-S6 into mRNA-LNPs relative to lipid content reduced particle size from 84.5 ± 1 to 67.9 ± 0.8 nm, elevated cellular uptake, and improved endosomal escape. These traits culminate in an increase in in cellula transfection from 24.2 ± 1.6% to 98.7 ± 0.6%. When injected intravenously into healthy BALB/c mice, the optimized COE-S6-doped mRNA-LNPs boost in vivo luciferase expression by 1.75-fold. Additionally, COE-S6-doped mRNA-LNPs exhibit fluorogenic properties, enabling intracellular mechanistic studies via confocal microscopy. This simple method enhances the properties of mRNA-LNPs with minimal COE quantities, offering a novel strategy to improve existing LNP formulations and provide optical reporting capabilities, essential for expediting drug discovery and delivery.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2405048"},"PeriodicalIF":10.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0