Rosa Bellavita, Teresa Barra, Simone Braccia, Marina Prisco, Salvatore Valiante, Assunta Lombardi, Linda Leone, Jessica Pisano, Rodolfo Esposito, Flavia Nastri, Gerardino D’Errico, Annarita Falanga and Stefania Galdiero*,
{"title":"Engineering Multifunctional Peptide-Decorated Nanofibers for Targeted Delivery of Temozolomide across the Blood–Brain Barrier","authors":"Rosa Bellavita, Teresa Barra, Simone Braccia, Marina Prisco, Salvatore Valiante, Assunta Lombardi, Linda Leone, Jessica Pisano, Rodolfo Esposito, Flavia Nastri, Gerardino D’Errico, Annarita Falanga and Stefania Galdiero*, ","doi":"10.1021/acs.molpharmaceut.4c0112510.1021/acs.molpharmaceut.4c01125","DOIUrl":null,"url":null,"abstract":"<p >A nanoplatform based on self-assembling peptides was developed with the ability to effectively transport and deliver a wide range of moieties across the blood–brain barrier (BBB) for the treatment of glioblastoma. Its surface was functionalized to have a targeted release of TMZ thanks to the targeting peptide that binds to EGFRvIII, which is overexpressed on tumor cells, and gH625, which acts as an enhancer of penetration. Furthermore, the on-demand release of TMZ was achieved through matrix metalloproteinase-9 (MMP-9) cleavage. Nanofibers were characterized for their stability, critical aggregation concentration, and morphology. Next, the effect on both 2D and 3D glioblastoma/astrocytoma (U-87) and glioma (U-118) cell lines was evaluated. The Annexin V/Propidium iodide showed an increase in necrotic and apoptotic cells, and the morphological analysis allowed to discover that both U-118 and U-87 spheroids are smaller in surface, perimeter, and Feret’s diameter when treated with NF-TMZ. The developed nanofiber was demonstrated to permeate the BBB <i>in vitro</i> in a 3D spheroidal biodynamic BBB model. Finally, there were no cytotoxic effects of nanofibers without the drug on spheroids, while a significant decrease in viability was observed when NF-TMZ was used. Overall, these results open new opportunities for the evaluation of the efficacy and safety of this nanoplatform in <i>in vivo</i> studies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 4","pages":"1920–1938 1920–1938"},"PeriodicalIF":4.5000,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.molpharmaceut.4c01125","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.4c01125","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Engineering Multifunctional Peptide-Decorated Nanofibers for Targeted Delivery of Temozolomide across the Blood–Brain Barrier
A nanoplatform based on self-assembling peptides was developed with the ability to effectively transport and deliver a wide range of moieties across the blood–brain barrier (BBB) for the treatment of glioblastoma. Its surface was functionalized to have a targeted release of TMZ thanks to the targeting peptide that binds to EGFRvIII, which is overexpressed on tumor cells, and gH625, which acts as an enhancer of penetration. Furthermore, the on-demand release of TMZ was achieved through matrix metalloproteinase-9 (MMP-9) cleavage. Nanofibers were characterized for their stability, critical aggregation concentration, and morphology. Next, the effect on both 2D and 3D glioblastoma/astrocytoma (U-87) and glioma (U-118) cell lines was evaluated. The Annexin V/Propidium iodide showed an increase in necrotic and apoptotic cells, and the morphological analysis allowed to discover that both U-118 and U-87 spheroids are smaller in surface, perimeter, and Feret’s diameter when treated with NF-TMZ. The developed nanofiber was demonstrated to permeate the BBB in vitro in a 3D spheroidal biodynamic BBB model. Finally, there were no cytotoxic effects of nanofibers without the drug on spheroids, while a significant decrease in viability was observed when NF-TMZ was used. Overall, these results open new opportunities for the evaluation of the efficacy and safety of this nanoplatform in in vivo studies.
期刊介绍：
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
