Pub Date : 2025-02-27eCollection Date: 2025-04-16DOI: 10.1021/acsbiomedchemau.4c00098
Mekedlawit T Setegne, Aidan T Cabral, Anushri Tiwari, Fangfang Shen, Hawa Racine Thiam, Laura M K Dassama
Biologics such as proteins, peptides, and oligonucleotides are powerful ligands to modulate challenging drug targets that lack readily accessible and "ligandable" pockets. However, the limited membrane permeance of biologics severely restricts their intracellular applications. Moreover, different cell types may exhibit varying levels of impermeability, and some delivery vehicles might be more sensitive to this variance. Erythroid lineage cells are especially challenging to deliver cargo to because of their unique cytoskeleton and the absence of endocytosis in mature erythrocytes. We recently employed a cell permeant miniature protein to deliver bioPROTACs to human umbilical cord blood derived erythroid progenitor cells (HUDEP-2) and primary hematopoietic stem (CD34+) cells (Shen et al., ACS Cent. Sci.2022, 8, 1695-1703). While successful, the low efficiency of delivery and lack of cell-type specificity limit use of bioPROTACs in vivo. In this work, we thoroughly evaluated the performance of various recently reported cell penetrating peptides (CPPs), CPP additives, bacterial toxins, and contractile injection systems for their ability to deliver cargo to erythroid precursor cells. We also explored how targeting receptors enriched on the erythroid cell surface might improve the efficiencies and specificities of these delivery vehicles. Our results reveal that certain vehicles exhibit improved efficiencies when directed to cell surface receptors while others do not benefit from this targeting strategy. Together, these findings advance our understanding of protein delivery to challenging cell types and illustrate some of the intricacies of cell-surface receptor targeting.
生物制剂如蛋白质、多肽和寡核苷酸是调节缺乏易接近和“可配体”口袋的具有挑战性的药物靶标的强大配体。然而，生物制剂有限的膜透性严重限制了其在细胞内的应用。此外，不同的细胞类型可能表现出不同程度的不渗透性，一些运载工具可能对这种差异更敏感。红系细胞由于其独特的细胞骨架和成熟红细胞内吞作用的缺失，尤其具有挑战性。我们最近使用了一种细胞渗透微型蛋白将生物protacs输送到人脐带血来源的红细胞祖细胞（HUDEP-2）和原代造血干细胞（CD34+）细胞（Shen et al., ACS Cent. Sci.2022, 8, 1695-1703）。虽然成功了，但低递送效率和缺乏细胞类型特异性限制了生物protacs在体内的使用。在这项工作中，我们全面评估了各种最近报道的细胞穿透肽（CPPs）、CPP添加剂、细菌毒素和收缩注射系统的性能，以评估它们向红细胞前体细胞输送货物的能力。我们还探讨了靶向红细胞表面富集的受体如何提高这些递送载体的效率和特异性。我们的研究结果表明，当定向到细胞表面受体时，某些载体表现出更高的效率，而其他载体则不能从这种靶向策略中获益。总之，这些发现促进了我们对蛋白质递送到挑战性细胞类型的理解，并说明了细胞表面受体靶向的一些复杂性。
{"title":"Engineering Cell-Specific Protein Delivery Vehicles for Erythroid Lineage Cells.","authors":"Mekedlawit T Setegne, Aidan T Cabral, Anushri Tiwari, Fangfang Shen, Hawa Racine Thiam, Laura M K Dassama","doi":"10.1021/acsbiomedchemau.4c00098","DOIUrl":"10.1021/acsbiomedchemau.4c00098","url":null,"abstract":"<p><p>Biologics such as proteins, peptides, and oligonucleotides are powerful ligands to modulate challenging drug targets that lack readily accessible and \"ligandable\" pockets. However, the limited membrane permeance of biologics severely restricts their intracellular applications. Moreover, different cell types may exhibit varying levels of impermeability, and some delivery vehicles might be more sensitive to this variance. Erythroid lineage cells are especially challenging to deliver cargo to because of their unique cytoskeleton and the absence of endocytosis in mature erythrocytes. We recently employed a cell permeant miniature protein to deliver bioPROTACs to human umbilical cord blood derived erythroid progenitor cells (HUDEP-2) and primary hematopoietic stem (CD34<sup>+</sup>) cells (Shen et al., ACS Cent. Sci.2022, 8, 1695-1703). While successful, the low efficiency of delivery and lack of cell-type specificity limit use of bioPROTACs <i>in vivo</i>. In this work, we thoroughly evaluated the performance of various recently reported cell penetrating peptides (CPPs), CPP additives, bacterial toxins, and contractile injection systems for their ability to deliver cargo to erythroid precursor cells. We also explored how targeting receptors enriched on the erythroid cell surface might improve the efficiencies and specificities of these delivery vehicles. Our results reveal that certain vehicles exhibit improved efficiencies when directed to cell surface receptors while others do not benefit from this targeting strategy. Together, these findings advance our understanding of protein delivery to challenging cell types and illustrate some of the intricacies of cell-surface receptor targeting.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 2","pages":"268-282"},"PeriodicalIF":3.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050648","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}
Pub Date : 2025-02-25eCollection Date: 2025-04-16DOI: 10.1021/acsbiomedchemau.5c00042
Paul D Goring, Amelia Newman, Christopher W Jones, Shelley D Minteer
{"title":"Celebrating 5 Years of the ACS Au Journal Family.","authors":"Paul D Goring, Amelia Newman, Christopher W Jones, Shelley D Minteer","doi":"10.1021/acsbiomedchemau.5c00042","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00042","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 2","pages":"235-237"},"PeriodicalIF":3.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999434","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}
Tai-Ping Zhou, Yakun Fan, Jinyan Zhang and Binju Wang*,
{"title":"","authors":"Tai-Ping Zhou, Yakun Fan, Jinyan Zhang and Binju Wang*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144399962","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":"","authors":"Rokas Gerulskis, and , Shelley D. Minteer*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144400499","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":"","authors":"Disha Kashyap, and , Michael J. Booth*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144400526","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}
Jessica R. Kenneson, Christina Papini, Su Tang, Kathy Huynh, Chun-Hui Zhang, William L. Jorgensen and Karen S. Anderson*,
{"title":"","authors":"Jessica R. Kenneson, Christina Papini, Su Tang, Kathy Huynh, Chun-Hui Zhang, William L. Jorgensen and Karen S. Anderson*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144400530","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}
Kevin C. Wang, Tiana L. Young, Jingan Chen, Shannon N. Tsai, Yue Xu, Andrew J. Varley, Nicholas C. Solek, Fanglin Gong, Rick X. Z. Lu, Basil P. Hubbard and Bowen Li*,
{"title":"","authors":"Kevin C. Wang, Tiana L. Young, Jingan Chen, Shannon N. Tsai, Yue Xu, Andrew J. Varley, Nicholas C. Solek, Fanglin Gong, Rick X. Z. Lu, Basil P. Hubbard and Bowen Li*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144399954","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":"","authors":"Joanna Afokai Quaye, and , Giovanni Gadda*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144400513","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":"","authors":"Kouichi Shiraishi*, and , Masayuki Yokoyama, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 1","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144400516","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号