{"title":"Multifunctional Tandem Peptide Mediates Targeted siRNA Delivery to Ovarian Cancer Cells.","authors":"Kharimat Lora Alatise, Timothy Samec, Carleigh Coffin, Serena Gilmore, Anthony Hazelton, Ruxi Xia, Chloe Jones, Angela Alexander-Bryant","doi":"10.1021/acsabm.4c01545","DOIUrl":"10.1021/acsabm.4c01545","url":null,"abstract":"<p><p>Fusogenic peptides have been developed to enhance the delivery efficiency of nucleic acids such as small interfering RNAs (siRNAs). Fusogenic peptides can protect nucleic acids from degradation and facilitate endosomal escape, but their systemic delivery capabilities remain unrefined. Active targeting of delivery systems to overexpressed cell receptors can be used to enhance cell- and tissue-specific delivery of therapeutic payloads while reducing off-target and systemic effects. We aimed to develop a targeted fusogenic (tandem) peptide, LHRHR-DIV3W, capable of targeting the luteinizing hormone-releasing hormone receptor (LHRHR), which is overexpressed in ovarian cancer cells and tissues. Characterization studies revealed that our tandem peptide, LHRHR-DIV3W, formed monodisperse nanocomplexes that protected siRNAs in physiological environments. We also demonstrated receptor-specific internalization of peptide-siRNA nanocomplexes in ovarian cancer cell lines with upregulated LHRHR expression. Furthermore, we observed that the inclusion of both the fusogenic DIV3W sequence and the LHRHR-targeting sequences in the tandem peptide enhanced receptor-specific siRNA internalization in ovarian cancer cells by up to 40% compared with the LHRHR-targeting peptide alone, indicating the necessity of combining both peptide regions. Finally, we demonstrated significant silencing of <i>CSNK2A1,</i> an oncogene overexpressed in ovarian cancer, in the ovarian cancer cell line OVCAR3. Our findings establish the use of a tandem peptide with cell-targeting and membrane-disruptive abilities as a delivery platform for nucleic acid therapies.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"4612-4620"},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging Technologies and Solutions for Chronic Wound Care and Diagnosis","authors":"Simon Matoori*, and , Elisabeth Engel*, ","doi":"10.1021/acsabm.5c0086510.1021/acsabm.5c00865","DOIUrl":"https://doi.org/10.1021/acsabm.5c00865https://doi.org/10.1021/acsabm.5c00865","url":null,"abstract":"","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 6","pages":"4413–4415 4413–4415"},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanotubular Gradients on Titanium: High-Throughput Screening of Nanoscale Architectures of Variable Topographical Complexity.","authors":"Ryan Berthelot, Fabio Variola","doi":"10.1021/acsabm.5c00697","DOIUrl":"https://doi.org/10.1021/acsabm.5c00697","url":null,"abstract":"<p><p>Advancements in cell-instructive biomaterials hinge on the precise design of their nanoscale topography, a critical factor in controlling cell-surface interactions. Nanofabrication techniques such as e-beam and nanoimprint lithography enable accurate nanopatterning on a wide range of materials. However, their limited applicability and scalability to medically relevant metals such as titanium, hinder the creation and modulation of precisely designed nanotopographies on metallic substrates to investigate structure-function relationships and clinical translation of nanotopographical surfaces for biomedical implants. In this context, anodization is a cost-effective, scalable method to nanopattern titanium and its alloys, producing arrays of TiO<sub>2</sub> nanotubes with precisely controlled diameters. Despite the significant advances in the understanding of how cells sense and respond to nanotubular surfaces, traditional diameter-focused research reliant on single-sized nanostructures restricts analysis to a narrow set of geometrical parameters and often overlook the spatial arrangement of nanotubes. To address these limitations, this study capitalizes on anodization to create scalable nanotubular gradients on titanium, introducing a high-throughput platform to explore the cellular response to a wide range of nanotopographical configurations within a single sample. Utilizing spatial metrics such as lacunarity, entropy, and fractal dimension, we characterized the structural complexity of the nanotubular surfaces, emphasizing geometrical considerations beyond the nanotube diameter in evaluating cellular response. In vitro assays with human MG63 osteoblastic cells revealed that more disordered, high-entropy regions significantly enhance cellular spreading and proliferation while promoting early osteogenic differentiation, evidenced by elevated RUNX2 and osteocalcin (OCN) expression. In contrast, mitochondrial activation and longer-term mineral deposition are elicited by more ordered nanotubular arrays. By streamlining the screening of nanotopographical features and enabling reproduction of user-selected designs as homogeneous surfaces, this gradient-based approach deepens mechanistic insights into structure-function relationships governing MG63 cell response to anodized titanium and offers a translatable framework for designing and evaluating nanotubular surfaces, shortening the gap between in vitro research and clinical applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clara Dourado Fernandes*, Alina Grünewald, Zoya Hadzhieva, Bruno F. Oechsler, Claudia Sayer, Pedro H. Hermes de Araújo* and Aldo R. Boccaccini*,
{"title":"","authors":"Clara Dourado Fernandes*, Alina Grünewald, Zoya Hadzhieva, Bruno F. Oechsler, Claudia Sayer, Pedro H. Hermes de Araújo* and Aldo R. Boccaccini*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c00176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144425843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Donya Esmaeilpour*, Matineh Ghomi, Ehsan Nazarzadeh Zare* and Mika Sillanpää*,
{"title":"","authors":"Donya Esmaeilpour*, Matineh Ghomi, Ehsan Nazarzadeh Zare* and Mika Sillanpää*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c00489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144425848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zitong Zhu, Huan Wang*, Yanjie Zhang, Mengmeng Liu and Jinsong Ren*,
{"title":"","authors":"Zitong Zhu, Huan Wang*, Yanjie Zhang, Mengmeng Liu and Jinsong Ren*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c00683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144425893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gold Nanoparticle-Assisted CRISPR-Cas12a-Based Activity Assay for Highly Sensitive Detection of Trypsin.","authors":"Sathishkumar Munusamy, Haiyan Zheng, Jun Chen, Shuo Zhou, Juanhua Kong, Rana Jahani, Yuan Zhao, Xiyun Guan","doi":"10.1021/acsabm.5c00854","DOIUrl":"https://doi.org/10.1021/acsabm.5c00854","url":null,"abstract":"<p><p>Proteases play important roles in diverse physiological processes, and their malfunction has been implicated in various conditions and diseases. Therefore, development of sensitive methods for protease detection in clinical samples is highly desired for disease diagnosis. Herein, we report an ultrasensitive and selective CRISPR-Cas12a based fluorescent assay for trypsin activity measurement. By taking advantage of the signal amplification brought by a unique magnetic bead-gold nanoparticle assembly, which carries the peptide substrate and tens to hundreds of DNA molecules per peptide molecule, trypsin can be detected with a limit of detection reaching as low as 0.13 ng/mL. Furthermore, the sensor selectivity study was performed by examining several biomolecules commonly present in biological samples, including bovine serum albumin (BSA), human serum albumin (HSA), DNase, RNase, chymotrypsin, elastase, and thrombin. Moreover, trypsin inhibition and serum sample analysis were successfully carried out. Given the ultrahigh sensitivity, the CRISPR-based trypsin activity assay developed in this work can be used as a generic platform for developing sensors for other proteases, offering the potential as a noninvasive/minimally invasive tool for clinical diagnosis.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"","authors":"Archana, Anil Kumar and Pratima R Solanki*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c00329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144357234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}