Li Liang , Ning Wang , Xiang Li , Zhuan Zhang , Zhu Zhu , Yan Zhuo , Xiaohe Jiang , Jie Wang , Cong Guo , Shiyan Guo , Pinghong Zhou , Yan Zhu , Yong Gan , Miaorong Yu
{"title":"通过外泌体形状工程实现内质网靶向递送和增强抗癌功效","authors":"Li Liang , Ning Wang , Xiang Li , Zhuan Zhang , Zhu Zhu , Yan Zhuo , Xiaohe Jiang , Jie Wang , Cong Guo , Shiyan Guo , Pinghong Zhou , Yan Zhu , Yong Gan , Miaorong Yu","doi":"10.1016/j.nantod.2024.102377","DOIUrl":null,"url":null,"abstract":"<div><p>Exosomes are nanoscale extracellular vesicles that have become pivotal in advancing targeted drug delivery strategies for cancer therapy. In this study, we conducted a comparative analysis of the intracellular targeting capabilities of differently shaped exosomes, including milk exosome nanorods (MR), ginger exosome nanorods (GR), and cancer cell exosome nanorods (HR), compared to their spherical counterparts. Our observations revealed that exosome nanorods demonstrated effective and sustained targeting of the endoplasmic reticulum (ER) within cancer cells, while exosome nanospheres were captured within lysosomes. Building on this principle, we chose milk-derived exosomes (mExo) for the <em>in vivo</em> research, engineering the surface of MR with folate to enhance their tumor-targeting efficacy. We demonstrated the effective accumulation of these folate-modified MR (FMR) around the ER in cancer cells, as validated in both orthotopic colorectal cancer (CRC) tissues and human CRC biopsy samples. Furthermore, when loaded with curcumin (Cur), the FMR@Cur exhibited remarkable efficacy in suppressing tumors in orthotopic CRC mouse models. This effect is attributed to the targeted delivery of FMR@Cur to the ER, leading to enhanced ER-stress induced apoptosis. Overall, our study underscores the pivotal role of shape engineering in exosome-mediated drug delivery, offering novel insights and paving the way for innovative strategies to enhance the precision of intracellular drug targeting in cancer therapy.</p></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":null,"pages":null},"PeriodicalIF":13.2000,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Shape Engineering of Exosomes for Endoplasmic Reticulum-Targeted Delivery and Amplified Anticancer Efficacy\",\"authors\":\"Li Liang , Ning Wang , Xiang Li , Zhuan Zhang , Zhu Zhu , Yan Zhuo , Xiaohe Jiang , Jie Wang , Cong Guo , Shiyan Guo , Pinghong Zhou , Yan Zhu , Yong Gan , Miaorong Yu\",\"doi\":\"10.1016/j.nantod.2024.102377\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Exosomes are nanoscale extracellular vesicles that have become pivotal in advancing targeted drug delivery strategies for cancer therapy. In this study, we conducted a comparative analysis of the intracellular targeting capabilities of differently shaped exosomes, including milk exosome nanorods (MR), ginger exosome nanorods (GR), and cancer cell exosome nanorods (HR), compared to their spherical counterparts. Our observations revealed that exosome nanorods demonstrated effective and sustained targeting of the endoplasmic reticulum (ER) within cancer cells, while exosome nanospheres were captured within lysosomes. Building on this principle, we chose milk-derived exosomes (mExo) for the <em>in vivo</em> research, engineering the surface of MR with folate to enhance their tumor-targeting efficacy. We demonstrated the effective accumulation of these folate-modified MR (FMR) around the ER in cancer cells, as validated in both orthotopic colorectal cancer (CRC) tissues and human CRC biopsy samples. Furthermore, when loaded with curcumin (Cur), the FMR@Cur exhibited remarkable efficacy in suppressing tumors in orthotopic CRC mouse models. This effect is attributed to the targeted delivery of FMR@Cur to the ER, leading to enhanced ER-stress induced apoptosis. Overall, our study underscores the pivotal role of shape engineering in exosome-mediated drug delivery, offering novel insights and paving the way for innovative strategies to enhance the precision of intracellular drug targeting in cancer therapy.</p></div>\",\"PeriodicalId\":395,\"journal\":{\"name\":\"Nano Today\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":13.2000,\"publicationDate\":\"2024-06-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nano Today\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1748013224002330\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nano Today","FirstCategoryId":"88","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1748013224002330","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
外泌体是一种纳米级细胞外囊泡,在推进癌症治疗的靶向给药策略方面发挥着举足轻重的作用。在这项研究中,我们比较分析了不同形状的外泌体(包括牛奶外泌体纳米棒(MR)、生姜外泌体纳米棒(GR)和癌细胞外泌体纳米棒(HR))与球形外泌体的胞内靶向能力。我们的观察结果表明,外泌体纳米棒能有效、持续地靶向癌细胞内的内质网(ER),而外泌体纳米球则能捕获溶酶体。基于这一原理,我们选择了源于牛奶的外泌体(mExo)进行体内研究,用叶酸对MR表面进行工程处理,以增强其肿瘤靶向功效。我们证明了这些叶酸修饰的MR(FMR)在癌细胞ER周围的有效聚集,这在正位结直肠癌(CRC)组织和人类CRC活检样本中都得到了验证。此外,当载入姜黄素(Cur)时,FMR@Cur 对抑制正位 CRC 小鼠模型中的肿瘤具有显著疗效。这种效果归功于 FMR@Cur 对 ER 的靶向递送,从而增强了 ER 压力诱导的细胞凋亡。总之,我们的研究强调了形状工程在外泌体介导的药物递送中的关键作用,为提高癌症治疗中细胞内药物靶向的精确性提供了新的见解,并为创新策略铺平了道路。
Shape Engineering of Exosomes for Endoplasmic Reticulum-Targeted Delivery and Amplified Anticancer Efficacy
Exosomes are nanoscale extracellular vesicles that have become pivotal in advancing targeted drug delivery strategies for cancer therapy. In this study, we conducted a comparative analysis of the intracellular targeting capabilities of differently shaped exosomes, including milk exosome nanorods (MR), ginger exosome nanorods (GR), and cancer cell exosome nanorods (HR), compared to their spherical counterparts. Our observations revealed that exosome nanorods demonstrated effective and sustained targeting of the endoplasmic reticulum (ER) within cancer cells, while exosome nanospheres were captured within lysosomes. Building on this principle, we chose milk-derived exosomes (mExo) for the in vivo research, engineering the surface of MR with folate to enhance their tumor-targeting efficacy. We demonstrated the effective accumulation of these folate-modified MR (FMR) around the ER in cancer cells, as validated in both orthotopic colorectal cancer (CRC) tissues and human CRC biopsy samples. Furthermore, when loaded with curcumin (Cur), the FMR@Cur exhibited remarkable efficacy in suppressing tumors in orthotopic CRC mouse models. This effect is attributed to the targeted delivery of FMR@Cur to the ER, leading to enhanced ER-stress induced apoptosis. Overall, our study underscores the pivotal role of shape engineering in exosome-mediated drug delivery, offering novel insights and paving the way for innovative strategies to enhance the precision of intracellular drug targeting in cancer therapy.
期刊介绍:
Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.