{"title":"利用脂质吉西他滨纳米治疗策略解决化疗耐药性问题,有效治疗胰腺癌","authors":"Jiawei Hong, Shiyun Xian, Shusen Zheng, Hangxiang Wang, Donghai Jiang","doi":"10.1007/s12274-024-6860-6","DOIUrl":null,"url":null,"abstract":"<p>Resistance to gemcitabine in pancreatic cancer poses a significant clinical challenge. Further investigation is warranted to assess whether nano-formulation strategy can be employed to enhance the sensitivity of resistant strains to gemcitabine therapy. In this study, using gemcitabine-resistant pancreatic cancer cell lines, we examined the therapeutic potential of a gemcitabine nanodelivery platform and assessed the ability to overcome drug resistance against resistant strains. Silencing of human equilibrative nucleoside transporter 1 (hENT1) led to reduced cellular uptake of gemcitabine, resulting in chemoresistance in pancreatic cancer. Gemcitabine nanoparticles circumvented the entry blockade caused by hENT1 silencing through endocytosis. Nanoparticle entry via clathrin-mediated endocytosis increased intracellular gemcitabine accumulation in gemcitabine-resistant pancreatic cancer cells. Moreover, gemcitabine nanoparticles are preferential <i>in vivo</i> delivery to tumor tissues, likely due to the enhanced permeability and retention effect. In comparison to free gemcitabine, gemcitabine nanoparticles demonstrate a more pronounced cytotoxic effect on gemcitabine-resistant pancreatic cancer cells, with favorable biosafety. This study improved the efficacy of gemcitabine through nanotechnology, providing a novel strategy to address gemcitabine-resistant pancreatic cancer.\n</p>","PeriodicalId":713,"journal":{"name":"Nano Research","volume":null,"pages":null},"PeriodicalIF":9.5000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Addressing chemoresistance with a lipid gemcitabine nanotherapeutic strategy for effective treatment of pancreatic cancer\",\"authors\":\"Jiawei Hong, Shiyun Xian, Shusen Zheng, Hangxiang Wang, Donghai Jiang\",\"doi\":\"10.1007/s12274-024-6860-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Resistance to gemcitabine in pancreatic cancer poses a significant clinical challenge. Further investigation is warranted to assess whether nano-formulation strategy can be employed to enhance the sensitivity of resistant strains to gemcitabine therapy. In this study, using gemcitabine-resistant pancreatic cancer cell lines, we examined the therapeutic potential of a gemcitabine nanodelivery platform and assessed the ability to overcome drug resistance against resistant strains. Silencing of human equilibrative nucleoside transporter 1 (hENT1) led to reduced cellular uptake of gemcitabine, resulting in chemoresistance in pancreatic cancer. Gemcitabine nanoparticles circumvented the entry blockade caused by hENT1 silencing through endocytosis. Nanoparticle entry via clathrin-mediated endocytosis increased intracellular gemcitabine accumulation in gemcitabine-resistant pancreatic cancer cells. Moreover, gemcitabine nanoparticles are preferential <i>in vivo</i> delivery to tumor tissues, likely due to the enhanced permeability and retention effect. In comparison to free gemcitabine, gemcitabine nanoparticles demonstrate a more pronounced cytotoxic effect on gemcitabine-resistant pancreatic cancer cells, with favorable biosafety. This study improved the efficacy of gemcitabine through nanotechnology, providing a novel strategy to address gemcitabine-resistant pancreatic cancer.\\n</p>\",\"PeriodicalId\":713,\"journal\":{\"name\":\"Nano Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.5000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nano Research\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1007/s12274-024-6860-6\",\"RegionNum\":2,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nano Research","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1007/s12274-024-6860-6","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Addressing chemoresistance with a lipid gemcitabine nanotherapeutic strategy for effective treatment of pancreatic cancer
Resistance to gemcitabine in pancreatic cancer poses a significant clinical challenge. Further investigation is warranted to assess whether nano-formulation strategy can be employed to enhance the sensitivity of resistant strains to gemcitabine therapy. In this study, using gemcitabine-resistant pancreatic cancer cell lines, we examined the therapeutic potential of a gemcitabine nanodelivery platform and assessed the ability to overcome drug resistance against resistant strains. Silencing of human equilibrative nucleoside transporter 1 (hENT1) led to reduced cellular uptake of gemcitabine, resulting in chemoresistance in pancreatic cancer. Gemcitabine nanoparticles circumvented the entry blockade caused by hENT1 silencing through endocytosis. Nanoparticle entry via clathrin-mediated endocytosis increased intracellular gemcitabine accumulation in gemcitabine-resistant pancreatic cancer cells. Moreover, gemcitabine nanoparticles are preferential in vivo delivery to tumor tissues, likely due to the enhanced permeability and retention effect. In comparison to free gemcitabine, gemcitabine nanoparticles demonstrate a more pronounced cytotoxic effect on gemcitabine-resistant pancreatic cancer cells, with favorable biosafety. This study improved the efficacy of gemcitabine through nanotechnology, providing a novel strategy to address gemcitabine-resistant pancreatic cancer.
期刊介绍:
Nano Research is a peer-reviewed, international and interdisciplinary research journal that focuses on all aspects of nanoscience and nanotechnology. It solicits submissions in various topical areas, from basic aspects of nanoscale materials to practical applications. The journal publishes articles on synthesis, characterization, and manipulation of nanomaterials; nanoscale physics, electrical transport, and quantum physics; scanning probe microscopy and spectroscopy; nanofluidics; nanosensors; nanoelectronics and molecular electronics; nano-optics, nano-optoelectronics, and nano-photonics; nanomagnetics; nanobiotechnology and nanomedicine; and nanoscale modeling and simulations. Nano Research offers readers a combination of authoritative and comprehensive Reviews, original cutting-edge research in Communication and Full Paper formats. The journal also prioritizes rapid review to ensure prompt publication.