Moon Jung Choi, Kang Chan Choi, Do Hyun Lee, Hwa Yeon Jeong, Seong Jae Kang, Min Woo Kim, In Ho Jeong, Young Myoung You, Jin Suk Lee, Yeon Kyung Lee, Chan Su Im, Yong Serk Park
{"title":"利用cd47工程细胞衍生的纳米平台靶向EGF受体治疗癌症。","authors":"Moon Jung Choi, Kang Chan Choi, Do Hyun Lee, Hwa Yeon Jeong, Seong Jae Kang, Min Woo Kim, In Ho Jeong, Young Myoung You, Jin Suk Lee, Yeon Kyung Lee, Chan Su Im, Yong Serk Park","doi":"10.2147/NSA.S352038","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle.</p><p><strong>Methods: </strong>The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR.</p><p><strong>Results: </strong>The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs.</p><p><strong>Discussion: </strong>These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.</p>","PeriodicalId":18881,"journal":{"name":"Nanotechnology, Science and Applications","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2022-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/95/nsa-15-17.PMC9270928.pdf","citationCount":"2","resultStr":"{\"title\":\"EGF Receptor-Targeting Cancer Therapy Using CD47-Engineered Cell-Derived Nanoplatforms.\",\"authors\":\"Moon Jung Choi, Kang Chan Choi, Do Hyun Lee, Hwa Yeon Jeong, Seong Jae Kang, Min Woo Kim, In Ho Jeong, Young Myoung You, Jin Suk Lee, Yeon Kyung Lee, Chan Su Im, Yong Serk Park\",\"doi\":\"10.2147/NSA.S352038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle.</p><p><strong>Methods: </strong>The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR.</p><p><strong>Results: </strong>The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs.</p><p><strong>Discussion: </strong>These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.</p>\",\"PeriodicalId\":18881,\"journal\":{\"name\":\"Nanotechnology, Science and Applications\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2022-07-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/95/nsa-15-17.PMC9270928.pdf\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanotechnology, Science and Applications\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/NSA.S352038\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"NANOSCIENCE & NANOTECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanotechnology, Science and Applications","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/NSA.S352038","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}
EGF Receptor-Targeting Cancer Therapy Using CD47-Engineered Cell-Derived Nanoplatforms.
Introduction: Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle.
Methods: The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR.
Results: The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs.
Discussion: These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.
期刊介绍:
Nanotechnology, Science and Applications is an international, peer-reviewed, Open Access journal that focuses on the science of nanotechnology in a wide range of industrial and academic applications. The journal is characterized by the rapid reporting of reviews, original research, and application studies across all sectors, including engineering, optics, bio-medicine, cosmetics, textiles, resource sustainability and science. Applied research into nano-materials, particles, nano-structures and fabrication, diagnostics and analytics, drug delivery and toxicology constitute the primary direction of the journal.