Helena Freire Haddad, Emily F Roe, Vinicius Xie Fu, Elizabeth J Curvino, Joel H Collier
{"title":"Multi-Target Peptide Nanofiber Immunotherapy Diminishes Complement Anaphylatoxin Activity in Acute Inflammation.","authors":"Helena Freire Haddad, Emily F Roe, Vinicius Xie Fu, Elizabeth J Curvino, Joel H Collier","doi":"10.1002/adhm.202402546","DOIUrl":"10.1002/adhm.202402546","url":null,"abstract":"<p><p>The anaphylatoxins C3a and C5a are products of the complement cascade that play important and interrelated roles in health and disease. Both are potential targets for anti-inflammatory active immunotherapies in which a patient's own immune system is stimulated to produce therapeutic immune responses against problematic self-molecules. However, the complex and time-dependent interrelations between the two molecules make dual targeting challenging. To investigate a dual-target active immunotherapy against C3a and C5a and to systematically study the effect of varied degrees of responses against both targets, the study employed self-assembled peptide immunogens capable of displaying a broad range of epitope compositions and Design-of-Experiments (DoE) approaches. Peptide nanofibers contained B-cell epitopes of C3a and C5a in defined quantities, and intranasal immunization raised systemic and mucosal immunity against each target. In a lipopolysaccharide-induced model of sepsis, increasing anti-C5a responses are protective, whereas increasing anti-C3a responses are detrimental, and survival rates are negatively correlated with anti-C3a/anti-C5a IgG titer ratio. This work highlights the interplay between the two molecules by making use of a modular, defined, and easily adjusted biomaterial-based active immunotherapy platform.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402546"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bo Li, Xinlei Yu, Xin Lu, Xianshun Sun, Yuanzhong Kai, Longjiu Cheng, Hongping Zhou, Yupeng Tian, Dandan Li
{"title":"Advancing Two-Photon Photodynamic Therapy Over NIR-II Excitable Conjugated Microporous Polymer with NIR-I Emission.","authors":"Bo Li, Xinlei Yu, Xin Lu, Xianshun Sun, Yuanzhong Kai, Longjiu Cheng, Hongping Zhou, Yupeng Tian, Dandan Li","doi":"10.1002/adhm.202402274","DOIUrl":"10.1002/adhm.202402274","url":null,"abstract":"<p><p>The availability of second near-infrared (NIR-II) excitable two-photon photosensitizers with NIR-I emission for efficient photodynamic therapy (PDT) is limited by challenges in molecular design. In this study, a NIR-II light-excitable two-photon conjugated microporous polymer (Tph-Dbd) with emission in the NIR-I region is developed. The large conjugated system and delocalized electronic structures endow Tph-Dbd with a large two-photon absorption cross-section under NIR-II light excitation. Moreover, the efficient electron acceptor and donor units within the π-conjugated backbones result in NIR-I emission for high signal-to-background ratio imaging, as well as separated highest occupied molecular orbital and lowest unoccupied molecular orbital distributions for excellent singlet oxygen generation ability. The excellent NIR-II excitable two-photon absorption activity, NIR-I emission, good biocompatibility, and high photostability allow Tph-Dbd to be used for efficient in vitro fluorescence imaging guided PDT. Moreover, the impressive photothermal effect of Tph-Dbd can overcome the limitations of PDT in the treatment of hypoxic tumors. This study highlights a strategy for designing NIR-II excitable two-photon photosensitizers for advanced PDT.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402274"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491358","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}
{"title":"Early Diagnosis of Liver Injury and Real-Time Evaluation of Photothermal Therapy Efficacy with a Viscosity-Responsive NIR-II Smart Molecule.","authors":"Qi Zan, Li Fan, Wenjing Lu, Yuewei Zhang, Yunong Huang, Xue Yu, Yahong Han, Ruiping Zhang, Chuan Dong, Shaomin Shuang","doi":"10.1002/adhm.202402614","DOIUrl":"10.1002/adhm.202402614","url":null,"abstract":"<p><p>The early diagnosis of liver injury and in situ real-time monitoring of tumor therapy efficacy are important for the enhancement of personalized precision therapy but remain challenging due to the lack of reliable in vivo visualization tools with integrated diagnostic, therapeutic, and efficacy monitoring functions. Herein, a smart second near-infrared window (NIR-II) molecule (BITX-OH) is rationally designed for diagnosis and therapy by vinyl-bridging hydroxyl diphenyl xanthine unit and benzo[cd]indolium skeleton. BITX-OH exhibits high selectivity and sensitivity toward viscosity, exhibiting a significant enhancement (1167-fold) in NIR-II fluorescence at 962 nm. With the assistance of BITX-OH and NIR-II fluorescence imaging, early diagnosis and therapeutic evaluation of non-alcoholic fatty liver (NAFL), as well as in-site real-time monitoring of hepatic fibrosis (HF) in live mice have been successfully achieved, which is at least several hours earlier than the typical clinical test. Notably, BITX-OH displays excellent photothermal conversion efficiency when exposed to an 808 nm laser, which can induce tumor ablation and increase viscosity, thereby enhancing NIR-II fluorescence for the real-time evaluation of photothermal therapy (PTT). This viscosity-based \"self-monitoring\" strategy provides a convenient and reliable platform for timely obtaining therapeutic feedback to avoid over- or under-treatment, thus enabling personalized precision therapy.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402614"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491366","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}
{"title":"Fabrication of MnO<sub>2</sub>-Modified Decellularized Tendon Membrane for Enhancing Tendon Repair.","authors":"Wanqing Lun, Huajun Wang, Mengyuan Li, Jiuzhi Ma, Yilin Ding, Xiaofei Zheng, Xiaodong Cao, Qingtao Li","doi":"10.1002/adhm.202402584","DOIUrl":"10.1002/adhm.202402584","url":null,"abstract":"<p><p>Repairing tendon/ligament injuries is a major challenge in sports medicine. It has been reported that tendon injury healing is hindered by massive production of reactive oxygen species (ROS). Manganese oxides nanoparticles are generally non-toxic, can scavenge ROS, promote tissue regeneration, and hold promise for sustainable nanotechnologies. However, the effective and safe integration of MnO<sub>2</sub> nanoparticles on decellularized scaffold mediating tissue repair is still a great challenge. To address these issues, an in situ MnO<sub>2</sub>-modified decellularized scaffold is developed to enhance tendon regeneration through improving microenvironment. The decellularized fibrous membrane is designed and prepared using the central tendon of the porcine diaphragm. Then MnO<sub>2</sub> nanozymes are in situ grown on the collagen fibers using tannic acid (TA) as cross-linking agent and reducing agent. The results showed that MnO<sub>2</sub>-modified scaffold eliminates excessive accumulation of ROS in cells, protects mitochondrial, and maintains the phenotype of tendon cells in an oxidative stress environment. Notably, it is found that the MnO<sub>2</sub>-modified scaffold exhibits good biocompatibility and is able to promote the tendon healing in the rat patellar tendon defect model. Altogether, this study confirmed that this nanozyme-functionalized decellularized extracellular matrix effectively enhanced tendon repair by scavenging ROS, which provides new strategies for enhancing tendon regeneration.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402584"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566632","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}
Yue Liu, Shang Chen, Haoyan Huang, Adam C Midgley, Zhibo Han, Zhong-Chao Han, Qiong Li, Zongjin Li
{"title":"Ligand-Tethered Extracellular Vesicles Mediated RNA Therapy for Liver Fibrosis.","authors":"Yue Liu, Shang Chen, Haoyan Huang, Adam C Midgley, Zhibo Han, Zhong-Chao Han, Qiong Li, Zongjin Li","doi":"10.1002/adhm.202403068","DOIUrl":"10.1002/adhm.202403068","url":null,"abstract":"<p><p>Liver fibrosis poses a significant global health burden, in which hepatic stellate cells (HSCs) play a crucial role. Targeted nanomedicine delivery systems directed at HSCs have shown immense potential in the treatment of liver fibrosis. Herein, a bioinspired material, engineered therapeutic miR-181a-5p (a miRNA known to inhibit fibrotic signaling pathways) and targeted moiety hyaluronic acid (HA) co-functionalized extracellular vesicles (EVs) are developed. HA is incorporated onto the surface of EVs using DSPE-PEG as a linker, allowing preferential binding to CD44 receptors, which are overexpressed on activated HSCs. Our results confirmed enhanced cellular uptake and improved payload delivery, as evidenced by the increased intracellular abundance of miR-181a-5p in activated HSCs and fibrotic livers. HA-equipped EVs loaded with miR-181a-5p (DPH-EVs@miR) significantly reduce HSC activation and extracellular matrix (ECM) deposition by inhibiting the TGF-β/Smad signaling pathway, thus alleviating the progression of liver fibrosis. Additionally, DPH-EVs@miR improves liver function, ameliorates inflammatory infiltration, and mitigates hepatocyte apoptosis, demonstrating superior hepatic protective effects. Collectively, this study reports a prospective nanovesicle therapeutic platform loaded with therapeutic miRNA and targeting motifs for liver fibrosis. The biomarker-guided EV-engineering technology utilized in this study provides a promising tool for nanomedicine and precision medicine.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403068"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613003","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}
Eszter Mihaly, Neha Chellu, Shama R Iyer, Eileen Y Su, Dallas E Altamirano, Shaquielle T Dias, Warren L Grayson
{"title":"Neuromuscular Regeneration of Volumetric Muscle Loss Injury in Response to Agrin-Functionalized Tissue Engineered Muscle Grafts and Rehabilitative Exercise.","authors":"Eszter Mihaly, Neha Chellu, Shama R Iyer, Eileen Y Su, Dallas E Altamirano, Shaquielle T Dias, Warren L Grayson","doi":"10.1002/adhm.202403028","DOIUrl":"10.1002/adhm.202403028","url":null,"abstract":"<p><p>Neuromuscular deficits compound the loss of contractile tissue in volumetric muscle loss (VML). Two avenues for promoting recovery are neuromuscular junction (NMJ)-promoting substrates (e.g., agrin) and endurance exercise. Although mechanical stimulation enhances agrin-induced NMJ formation, the two modalities have yet to be evaluated combinatorially. It is hypothesized that the implantation of human myogenic progenitor-seeded tissue-engineered muscle grafts (hTEMGs) in combination with agrin treatment and/or exercise will enhance neuromuscular recovery after VML. The hTEMGs alone transplant into VML defects promote significant regeneration with minimal scarring. A sex-appropriate, low-intensity continuous running exercise paradigm increases acetylcholine receptor (AChR) cluster density in male mice twofold relative to hTEMG alone after 7 weeks of treadmill training (p < 0.05). To further promote neuromuscular recovery, agrin is incorporated into the scaffolds via covalent tethering. In vitro, agrin increases the proliferation of hMPs, and trends toward greater myogenic maturity and AChR clustering. Upon transplantation, both hTEMGs + agrin and hTEMGs + exercise induce near 100% recovery of muscle mass and increase twitch and tetanic force output (p > 0.05). However, agrin treatment in combination with exercise produces no additional benefit. These data highlight the unprecedented regenerative potential of using hTEMGs together with either agrin or exercise supplementation to treat VML injuries.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403028"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613015","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}
Kexin Fan, Qingyang Li, Yuping Qian, Ludan Zhang, Di Lu, Ling Zhu, Shouke Yan, Bowei Xu, Yuguang Wang
{"title":"Enhanced Photothermal Therapy under Low-Power Near-Infrared Irradiation Enabled by a Si-Cyclopentadithiophene-Based Organic Molecule.","authors":"Kexin Fan, Qingyang Li, Yuping Qian, Ludan Zhang, Di Lu, Ling Zhu, Shouke Yan, Bowei Xu, Yuguang Wang","doi":"10.1002/adhm.202403248","DOIUrl":"10.1002/adhm.202403248","url":null,"abstract":"<p><p>Due to the inadequate photothermal conversion efficiency (PCE), most photothermal agents (PTAs) have to be used under high-power near-infrared (NIR) irradiation, which significantly exceeds medical safety standards, for achieving effective photothermal therapy (PTT) in antitumor treatment. This significantly hinders practical PTT application. Herein, three acceptor-donor-acceptor(A-D-A)-type molecules are synthesized based on cyclopentadithiophene unit to develop effective PTAs. By incorporating the large-size Si atom in the A-D-A molecules, the photosensitizer displays an increased packing distance in the aggregate state, leading to a blue-shifted absorption spectrum that better matches the medial laser wavelength. Also, the Si incorporation strategy elevates the nonradiative decay rate constants (k<sub>nr</sub>) of the A-D-A photosensitizer, and thereby a further enhancement in PCE is achieved for the PTA. Consequently, the SiO-4F-based nanoparticles exhibited 64.23% PCE, with excellent biosafety and photothermal stability. Under NIR irradiation with medical safety (808 nm, 0.33 W cm<sup>-2</sup>), SiO-4F nanoparticles with 100 µg mL<sup>-1</sup> yield a death rate of over 91% for diverse tumor cells. Moreover, in vivo experiments, SiO-4F-based PTT effectively inhibited and eliminated tumors. These findings suggest that the Si-incorporated CDPT is promising for constructing effective A-D-A photosensitizers, enabling the PTT under NIR irradiation that meets medical safety standards.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403248"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646214","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}
{"title":"Casting New Light on the Retinol and Retinyl Palmitate Functions as Chemical Enhancers for Transdermal/Topical Drug Delivery.","authors":"Yun-Hao Ren, Qi Zhou, Yang Xu, Bei-Ning Xu, Peng Shu, Li-Hua Peng","doi":"10.1002/adhm.202402836","DOIUrl":"10.1002/adhm.202402836","url":null,"abstract":"<p><p>Retinol and retinyl palmitate, with excellent whitening and antioxidant activities, are widely used as essential functional ingredients in transdermal preparations and skincare products. Herein, for the first time, the influence and underlying mechanisms of retinol and retinyl palmitate on the skin penetration of caffeine are investigated. It is found that the penetration of caffeine is very significantly enhanced by retinol and retinyl palmitate with 2.83 and 2.57 folds, respectively. Mechanistic studies showed that they can disrupt the lipids of intercellular orderly arrangement and reduce the content of orthorhombic lattices in the skin, making the skin loose and the barrier function decreased. Furthermore, due to the formation of chemical bonds with the skin keratin, they have a strong affinity with the skin, changing the dense secondary structure of keratin with a reduced skin barrier effect. This study provides new evidence for the potential of retinol and retinyl palmitate as novel skin penetration enhancers with high safety that possess great potential for application in the transdermal delivery of pharmaceutical and cosmetic active substances.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402836"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708633","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}
Jihyun Kim, Seol-Ha Jeong, Brendan Craig Thibault, Javier Alejandro Lozano Soto, Hiroyuki Tetsuka, Surya Varchasvi Devaraj, Estefania Riestra, Yeongseok Jang, Jeong Wook Seo, Rafael Alejandro Cornejo Rodríguez, Lucia L Huang, Yuhan Lee, Ioana Preda, Sameer Sonkusale, Lance Fiondella, Jungmok Seo, Lorenzo Pirrami, Su Ryon Shin
{"title":"Large Scale Ultrafast Manufacturing of Wireless Soft Bioelectronics Enabled by Autonomous Robot Arm Printing Assisted by a Computer Vision-Enabled Guidance System for Personalized Wound Healing.","authors":"Jihyun Kim, Seol-Ha Jeong, Brendan Craig Thibault, Javier Alejandro Lozano Soto, Hiroyuki Tetsuka, Surya Varchasvi Devaraj, Estefania Riestra, Yeongseok Jang, Jeong Wook Seo, Rafael Alejandro Cornejo Rodríguez, Lucia L Huang, Yuhan Lee, Ioana Preda, Sameer Sonkusale, Lance Fiondella, Jungmok Seo, Lorenzo Pirrami, Su Ryon Shin","doi":"10.1002/adhm.202401735","DOIUrl":"10.1002/adhm.202401735","url":null,"abstract":"<p><p>A Customized wound patch for Advanced tissue Regeneration with Electric field (CARE), featuring an autonomous robot arm printing system guided by a computer vision-enabled guidance system for fast image recognition is introduced. CARE addresses the growing demand for flexible, stretchable, and wireless adhesive bioelectronics tailored for electrotherapy, which is suitable for rapid adaptation to individual patients and practical implementation in a comfortable design. The visual guidance system integrating a 6-axis robot arm enables scans from multiple angles to provide a 3D map of complex and curved wounds. The size of electrodes and the geometries of power-receiving coil are essential components of the CARE and are determined by a MATLAB simulation, ensuring efficient wireless power transfer. Three heterogeneous inks possessing different rheological behaviors can be extruded and printed sequentially on the flexible substrates, supporting fast manufacturing of large customized bioelectronic patches. CARE can stimulate wounds up to 10 mm in depth with an electric field strength of 88.8 mV mm<sup>-1</sup>. In vitro studies reveal the ability to accelerate cell migration by a factor of 1.6 and 1.9 for human dermal fibroblasts and human umbilical vein endothelial cells, respectively. This study highlights the potential of CARE as a clinical wound therapy method to accelerate healing.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2401735"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruhina Maeshima, Aristides D Tagalakis, Dafni Gyftaki-Venieri, Stuart A Jones, Philip D Rye, Anne Tøndervik, O Alexander H Åstrand, Stephen L Hart
{"title":"Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus.","authors":"Ruhina Maeshima, Aristides D Tagalakis, Dafni Gyftaki-Venieri, Stuart A Jones, Philip D Rye, Anne Tøndervik, O Alexander H Åstrand, Stephen L Hart","doi":"10.1002/adhm.202400510","DOIUrl":"10.1002/adhm.202400510","url":null,"abstract":"<p><p>Airway mucus is a major barrier to the delivery of lipid-based nanoparticles in chronic airway diseases such as cystic fibrosis (CF). Receptor-Targeted Nanocomplexes (RTN), comprise mixtures of cationic lipids and bifunctional peptides with receptor-targeting and nucleic acid packaging properties. The aim of this study is to improve the mucus-penetrating properties of cationic siRNA and mRNA RTNs by combining them with low molecular weight alginate oligosaccharides, OligoG and OligoM. Cationic RTNs formulated with either alginate become strongly anionic, while PEGylated messenger RNA (mRNA) and short interfering RNA (siRNA) RTNs remain cationic. Both alginates enhance mucus diffusion rates of cationic siRNA and mRNA RTNs in a static mucus barrier diffusion model, with OligoG particularly effective. PEGylation also enhance mucus diffusion rates of siRNA RTNs but not mRNA RTNs. Electron microscopy shows that RTNs remained intact after mucosal transit. The transfection efficiency of OligoM-coated mRNA RTNs is better than those coated with OligoG or PEG, and similar to cationic RTNs. In siRNA RTN transfections, OligoM is better than OligoG although 1% PEG is slightly better than both. The combination of cationic RTNs and alginate oligosaccharides represents a promising alternative to PEGylation for epithelial delivery of genetic therapies across the mucus barrier while retaining transfection efficiency.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2400510"},"PeriodicalIF":10.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}