ACS Biomaterials Science & Engineering最新文献

{"title":"Intranasal Delivery of Ivermectin Nanosystems as an Antitumor Agent: Focusing on Glioma Suppression.","authors":"Maiara Callegaro Velho, Valeria Luiza Winck, Camila da Silveira Mariot, Juliete Nathali Scholl, Augusto Ferreira Weber, Rita de Kássia Souza, Fernanda Visioli, Fabrício Figueiró, Monique Deon, Diogo André Pilger, Ruy Carlos Ruver Beck","doi":"10.1021/acsbiomaterials.5c00642","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00642","url":null,"abstract":"<p><p>Glioblastoma presents significant challenges in neuro-oncology due to its aggressive nature, drug resistance, and restrictions imposed by the blood-brain barrier. Ivermectin (IVM), known for its antiparasitic properties, has been highlighted as a promising treatment for tumors and an alternative therapy for glioma, although it exhibits low oral bioavailability. Therefore, we investigated the <i>in vivo</i> effect of IVM encapsulation in organic and inorganic nanosystems, first screened <i>in vitro</i> against different tumor cells and subsequently evaluated <i>in vitro</i> and <i>in vivo</i> glioma models. We produced IVM-loaded poly(ε-caprolactone) nanocapsules (IVM-NC) using the interfacial deposition method, and IVM-loaded nanostructured silica particles (IVM-MCM) by loading IVM into commercial MCM-41 silica using the incipient wetness method. IVM-NC had a nanometric size (190 nm), a unimodal size distribution (span <2), and a high encapsulation efficiency (100% at 1 mg/mL). IVM-MCM exhibited a well-organized hexagonal mesoporous structure and high drug loading (0.12 mg/mg). Nanoencapsulated IVM significantly reduced the viability of various cancer cell lines, particularly glioma cell lines, which led us to evaluate them in a preclinical glioma model. We implanted adult male Wistar rats with C6 cells. Intranasal delivery of IVM-NC (60 μg/rat/day for 10 days) resulted in a larger decrease in tumor size compared with the group treated with free IVM, along with histopathological improvements. Treatment with IVM-MCM did not decrease the tumor size. However, both treatments were well-tolerated, with no adverse effects on weight, biochemical, or hematological parameters, or lung histology. Furthermore, the effective equivalent dose of IVM (26 μg/kg) in the rat glioma model was lower than the approved human dose for parasitic infections. This study marks the first exploration of IVM delivery to the brain. In summary, nasal administration of nanoencapsulated IVM via nanocapsules presents a promising avenue for targeted therapy against glioblastoma, with potential implications for clinical translation.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264750","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":"Engineered Extracellular Vesicles for Tumor-Targeted Delivery of Therapeutic siRNA for Lung Cancer Therapy.","authors":"Rahmat Asfiya, Anjugam Paramanantham, Ragavi Premnath, Grace McCully, Fatimah Yousuf, Gregory Goetz, Akhil Srivastava","doi":"10.1021/acsbiomaterials.5c00434","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00434","url":null,"abstract":"<p><p>RNAi-based technologies offer the potential to treat cancer effectively, but safe and efficient RNA administration remains a barrier to their clinical adoption. In this study, we developed extracellular vesicles (EVs) and a gold nanoparticle (GNP)-based hybrid system for the targeted delivery of therapeutic siRNA. We used siRNA to silence the B7-H4 encoding gene (a B7 family immune checkpoint protein, gene <i>VTCN1</i>). The knockdown of B7-H4 inhibits proliferation, invasion, and migration in cancer cell lines and increases apoptosis levels. The standardized nanocomplex of GNPs and B7-H4 siRNA (GNPs-siR_B) was hybridized with EVs by a heat shock technique in the presence of CaCl₂ to form the EV-siR_B hybrid system. Furthermore, the system's ability to selectively deliver siRNA was examined in two Non-Small Cell Lung Cancer (NSCLC) cell lines, viz., H1299 and A549, as well as in a normal lung fibroblast cell line (MRC9). We found that the standard dose of EV-siR_B effectively knocked down B7-H4 in cancer cells H1299 and A549 and their spheroids. However, it was less effective in normal lung cells (MRC9). Finally, we demonstrated the antitumor therapeutic effect of the EV-siR_B complex in NSCLC xenograft models. The results from this study highlight the effectiveness of the hybrid EV-siR_B system in delivering therapeutic siRNA to tumor cells and open an avenue to explore the efficacy of the system in patient-derived NSCLC and other solid tumor models.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264749","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":"DDTC-Cu(I) Nano-MOF Induces Ferroptosis by Targeting SLC7A11/GPX4 Signal in Colorectal Cancer.","authors":"Juan Huang, Mingjing Yang, Xingyu Zhou, Jigang Luo, Xiaoxia Yan, Guanghui Lin, Shijie Li, Shihui Liu, Zhuoyue Song, Chunzhi Tang, Nenggui Xu, Tao Liu, Jian Liang","doi":"10.1021/acsbiomaterials.5c00680","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00680","url":null,"abstract":"<p><p>Drug repurposing has received increasing attention in the field of oncology drug development as an alternative strategy to de novo drug synthesis. Disulfiram (DSF) has a long history of clinical application in alcohol withdrawal, and recent studies have revealed that its metabolite diethyldithiocarbamate (DDTC) can be coordinated with copper ions in vivo to form Cu-DDTC complexes with anticancer activity. However, the insufficient in vivo stability of DSF remains a challenge. In this study, the nanomedicine Cu-BTC@DDTC with DDTC-Cu(I) chemical valence and polycrystalline structure was prepared by incorporation of DDTC into the nanosized metal-organic framework (MOF) Cu-BTC. The in vitro cellular evaluation results showed that Cu-BTC@DDTC exhibited high inhibition of tumor cell growth, migration, and invasion. Animal experiments on the xenograft tumor model further demonstrated the excellent antitumor activity and biosafety of Cu-BTC@DDTC, and the antitumor activity was found to be closely related to the regulation of the SLC7A11/GPX4 signaling pathway to induce ferroptosis. This study provides a feasible option for antitumor drug development based on a drug repurposing strategy.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256621","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":"","authors":"Swatilekha Hazra,&nbsp;Souradeep Dey,&nbsp;Biman B. Mandal* and Charanya Ramachandran*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":5.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.5c00200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144373866","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}

{"title":"","authors":"Annie Scutte,&nbsp;Kiram Harrison,&nbsp;Tyler Gregory,&nbsp;David Quashie Jr.,&nbsp;Subramanian Ramakrishnan and Jamel Ali*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":5.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.5c00223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144373874","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}

{"title":"","authors":"Yu-Bai Xiao,&nbsp;Linda Ravazzano,&nbsp;Maria Grano,&nbsp;Graziana Colaianni,&nbsp;Clair Baldock,&nbsp;Flavia Libonati* and Anna Tarakanova*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":5.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.5c00089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144373875","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}

{"title":"","authors":"Catherine A. Wu,&nbsp;Yuanjia Zhu and Y. Joseph Woo*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":5.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.4c01931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144373877","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}

{"title":"Addition of Microscale Topographies to Silk Fibroin Film Modulates Corneal Endothelial Cell Behavior.","authors":"Swatilekha Hazra, Souradeep Dey, Biman B Mandal, Charanya Ramachandran","doi":"10.1021/acsbiomaterials.5c00200","DOIUrl":"10.1021/acsbiomaterials.5c00200","url":null,"abstract":"<p><p>Biomimicry in tissue engineering has been used to improve the function of a structure by closely replicating the native architecture. One such method is the introduction of micro- and nanotopographical patterns on biomaterials that mimic the native extracellular environment to enhance cell behavior and function before and after clinical transplantation. Earlier studies from our laboratory had shown that silk fibroin films offer promising potential for corneal endothelial regeneration because of their optimum optical, mechanical, and functional properties. In this study, we hoped to improve upon the design by incorporating micropatterns that are present in the native tissue on the surface of silk films. Fibroin protein from <i>Antheraea assamensis</i> worms was used to prepare films with and without patterns (hexagons and microgrooves) on their surface. The mechanical and optical properties of these films were analyzed by measuring the Young's modulus and light transmittance in the visible spectrum. Cell adhesion and proliferation were determined using the MTT assay and Ki67 staining, respectively. Morphometric analysis of cell shape and size was performed using the ImageJ software, and the expression of markers was visualized and quantified using immunostaining and Western blot. Patterned films demonstrated enhanced elasticity, roughness, and hydrophilicity compared to flat films. No significant difference was observed in cell adhesion between the flat and patterned films. The percentage of proliferating cells was significantly reduced on the patterned films, especially on hexagons. The cell area and circularity on flat films were comparable to microgrooves, whereas cells on hexagons displayed larger and more variable sizes. Notably, the expression of Na-K ATPase (a critical pump protein) was significantly higher in cells grown on microgrooves than on other substrates. These findings suggest that incorporating simple micropatterns on the surface of silk fibroin films can improve the morphology and functional quality of corneal endothelial cells, providing insights into the development of biomaterial-based strategies for endothelial transplantation.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"3586-3596"},"PeriodicalIF":5.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950931","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":"Fe-Doped Carbon Dots Alleviated Rheumatoid Arthritis by Inhibiting Neutrophil NETosis and Autophagy.","authors":"Hesong Wang, Aimin Yan, Congmin Xia, Yue Zhang, Yali Zhou, Huaijuan Huang, Xun Gong, Kai Yuan, Guangrui Huang","doi":"10.1021/acsbiomaterials.4c01880","DOIUrl":"10.1021/acsbiomaterials.4c01880","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is an autoimmune disorder primarily affecting joints, characterized by high incidence rates and significantly impairing patients' quality of life. Neutrophils play a pivotal role in RA pathogenesis, making therapeutic interventions targeting neutrophil-mediated inflammatory cascades a promising strategy for RA treatment.</p><p><strong>Methods: </strong>Inspired by traditional Tibetan medicinal formulations, which typically combine metallic minerals and organic components, this study developed iron-doped carbon dots (MM-CDs) via a facile one-pot synthesis approach using magnetite (Cishi) and medicated leaven (Shenqu). The therapeutic efficacy of MM-CDs was subsequently evaluated in a mouse model of RA. The results indicated that MM-CDs effectively alleviated RA by disrupting neutrophil-induced inflammatory cascades. Specifically, MM-CDs inhibited NETosis, significantly downregulated myeloperoxidase (MPO), citrullinated histone H3 (Cit-H3), and peptidyl arginine deiminase 4 (PAD-4) in joint tissues (<i>P</i> < 0.05). Furthermore, MM-CDs modulated autophagy pathways, suppressing LC3B and Beclin-1 expression, thereby reducing neutrophil survival. Additionally, MM-CDs promoted apoptosis in neutrophils, evidenced by increased cleaved caspase-3/PARP expression and decreased Bcl-2 levels in LPS-stimulated neutrophils.</p><p><strong>Conclusion: </strong>This study demonstrates that MM-CDs represent a novel and effective therapeutic strategy for RA. Importantly, the treatment exhibited no liver or kidney toxicity in the RA mouse model, highlighting its potential for safe clinical translation.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"3666-3681"},"PeriodicalIF":5.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109031","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":"Development of a Sensory Neuron-Integrated Skin Spheroid Model for the Evaluation of Neuropeptide-Based Topical Delivery Systems.","authors":"Bianca Aparecida Martin, Juliana Viegas, Luciana Facco Dalmolin, Emerson de Souza Santos, Izabela Pereira Vatanabe, Sabrina Francesca Lisboa, Renata Fonseca Vianna Lopez, Bruno Sarmento","doi":"10.1021/acsbiomaterials.5c00141","DOIUrl":"10.1021/acsbiomaterials.5c00141","url":null,"abstract":"<p><p>The skin is a complex organ composed of multiple layers and diverse cell types, including keratinocytes, fibroblasts, adipocytes, and sensory neurons, which maintain its structural and functional integrity together. Conventional in vitro and ex vivo models help investigate drug permeation and selected biological effects. However, they are limited in replicating neural interactions critical for assessing the efficacy of neuropeptide-based therapies. To address this limitation, a sensory neuron-integrated skin spheroid (SS) model was established, incorporating key skin cell types and providing a rapid, adaptable, and physiologically relevant platform for screening the biological activity of topical delivery systems targeting neuronal pathways. The model's responsiveness was demonstrated using acetyl hexapeptide-3 (HEX-3), a neuropeptide that inhibits acetylcholine release. HEX-3 was internalized by spheroid cells, with preferential accumulation around sensory neurons, confirming targeted cellular uptake. In parallel, ex vivo human skin studies confirmed that HEX-3 can traverse the stratum corneum and accumulate in deeper layers. Treatment with this film enhanced skin hydration, reduced scaling, and improved the structural organization of the stratum corneum after 48 h. Functional assays using the SS model showed that HEX-3 treatment suppressed acetylcholine release, upregulated the antioxidant enzyme SOD2, and stimulated type I collagen synthesis. In aged skin samples, the application of HEX-3 significantly increased collagen levels. This effect was mirrored in the spheroid model, which reached collagen levels comparable to those of aged human skin upon treatment. These findings establish the SS model as a robust platform for evaluating the biological activity of neuropeptide-based topical therapies, offering valuable insights for developing advanced strategies for skin rejuvenation and repair.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"3503-3522"},"PeriodicalIF":5.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131790","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}