Hansol Lim , Gaeun Ma , Yunhwa Jeong , Jae-Hyeon Lee , Jun-Hyuck Lee , Seong-Bin Yang , Jeong Uk Choi , Ha Rin Kim , Jooho Park
{"title":"利用互补的肝素分子和原胺分子原位聚合纳米粒子对纳米粒子的肿瘤靶向策略,同时诱导铁变态反应和免疫性细胞死亡","authors":"Hansol Lim , Gaeun Ma , Yunhwa Jeong , Jae-Hyeon Lee , Jun-Hyuck Lee , Seong-Bin Yang , Jeong Uk Choi , Ha Rin Kim , Jooho Park","doi":"10.1016/j.nantod.2024.102355","DOIUrl":null,"url":null,"abstract":"<div><p>Antibody-drug conjugate (ADC)-based tumor-targeting therapies have demonstrated clinical success in selective drug delivery for cancer treatment. However, the effectiveness of these strategies is hindered by the low amount of loaded payload, lack of sustained efficacy, and insufficient therapeutic performance. In this study, we introduce a novel <em>in situ</em> aggregation-based targeting system using two combinable nanoparticles (NP) that leverage the biocompatible and specific interaction between complementary protamine and heparin molecules. To demonstrate it, we developed protamine-based nanoparticles (PPNC NP) containing cytotoxic negatively charged curcumin (NCur), and heparin-based nanoparticles (HDFe NP) encapsulating doxorubicin and Fe<sup>3+</sup>. The NP-NP treatment successfully formed aggregates at targeted tumor sites. Our findings demonstrate that the initial administration of PPNC NP effectively targets the tumor and the subsequent administration of complementary HDFe NPs results in their significant accumulation in the tumor tissue, directed by the ‘guidance effect’ of PPNC NPs. This sequence of events promotes the formation of <em>in situ</em> aggregates within the tumor tissue, leading to prolonged nanoparticle accumulation, ferroptosis and immunogenic cell death (ICD). In conclusion, our study demonstrates the effectiveness of a biocompatible and <em>in situ</em> aggregating nanoparticle-nanoparticle system as a solution for overcoming the limitations of current nanoparticle-based delivery systems.</p></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":null,"pages":null},"PeriodicalIF":13.2000,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tumor targeting in situ aggregation of nanoparticle-to-nanoparticle strategy to simultaneously induce ferroptosis and immunogenic cell death using complementary heparin and protamine molecules\",\"authors\":\"Hansol Lim , Gaeun Ma , Yunhwa Jeong , Jae-Hyeon Lee , Jun-Hyuck Lee , Seong-Bin Yang , Jeong Uk Choi , Ha Rin Kim , Jooho Park\",\"doi\":\"10.1016/j.nantod.2024.102355\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Antibody-drug conjugate (ADC)-based tumor-targeting therapies have demonstrated clinical success in selective drug delivery for cancer treatment. However, the effectiveness of these strategies is hindered by the low amount of loaded payload, lack of sustained efficacy, and insufficient therapeutic performance. In this study, we introduce a novel <em>in situ</em> aggregation-based targeting system using two combinable nanoparticles (NP) that leverage the biocompatible and specific interaction between complementary protamine and heparin molecules. To demonstrate it, we developed protamine-based nanoparticles (PPNC NP) containing cytotoxic negatively charged curcumin (NCur), and heparin-based nanoparticles (HDFe NP) encapsulating doxorubicin and Fe<sup>3+</sup>. The NP-NP treatment successfully formed aggregates at targeted tumor sites. Our findings demonstrate that the initial administration of PPNC NP effectively targets the tumor and the subsequent administration of complementary HDFe NPs results in their significant accumulation in the tumor tissue, directed by the ‘guidance effect’ of PPNC NPs. This sequence of events promotes the formation of <em>in situ</em> aggregates within the tumor tissue, leading to prolonged nanoparticle accumulation, ferroptosis and immunogenic cell death (ICD). In conclusion, our study demonstrates the effectiveness of a biocompatible and <em>in situ</em> aggregating nanoparticle-nanoparticle system as a solution for overcoming the limitations of current nanoparticle-based delivery systems.</p></div>\",\"PeriodicalId\":395,\"journal\":{\"name\":\"Nano Today\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":13.2000,\"publicationDate\":\"2024-06-10\",\"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/S174801322400210X\",\"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/S174801322400210X","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}
Tumor targeting in situ aggregation of nanoparticle-to-nanoparticle strategy to simultaneously induce ferroptosis and immunogenic cell death using complementary heparin and protamine molecules
Antibody-drug conjugate (ADC)-based tumor-targeting therapies have demonstrated clinical success in selective drug delivery for cancer treatment. However, the effectiveness of these strategies is hindered by the low amount of loaded payload, lack of sustained efficacy, and insufficient therapeutic performance. In this study, we introduce a novel in situ aggregation-based targeting system using two combinable nanoparticles (NP) that leverage the biocompatible and specific interaction between complementary protamine and heparin molecules. To demonstrate it, we developed protamine-based nanoparticles (PPNC NP) containing cytotoxic negatively charged curcumin (NCur), and heparin-based nanoparticles (HDFe NP) encapsulating doxorubicin and Fe3+. The NP-NP treatment successfully formed aggregates at targeted tumor sites. Our findings demonstrate that the initial administration of PPNC NP effectively targets the tumor and the subsequent administration of complementary HDFe NPs results in their significant accumulation in the tumor tissue, directed by the ‘guidance effect’ of PPNC NPs. This sequence of events promotes the formation of in situ aggregates within the tumor tissue, leading to prolonged nanoparticle accumulation, ferroptosis and immunogenic cell death (ICD). In conclusion, our study demonstrates the effectiveness of a biocompatible and in situ aggregating nanoparticle-nanoparticle system as a solution for overcoming the limitations of current nanoparticle-based delivery systems.
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.