{"title":"脂碘乳剂作为胰腺癌治疗的双重化疗增敏剂。","authors":"","doi":"10.1016/j.jconrel.2024.08.020","DOIUrl":null,"url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and limited treatment options. Concurrent chemoradiotherapy is considered beneficial to improve tumor control, but the low drug bioavailability at tumor site and the low radiation tolerance of surrounding healthy organs greatly limits its effectiveness. Lipiodol, a natural drug carrier used in clinical transarterial chemoembolization, has shown potential as a radiosensitizer due to its high Z element iodine composition. Thus, this study aims to repurpose lipiodol as a sensitizer to simultaneously enhance chemo- and radiotherapy for PDAC. To this end, a stable lipiodol emulsion (IOE) loaded with gemcitabine is designed using clinically approved surfactants. At in vivo level, IOE demonstrates better radiotherapeutic effect than existing nanoradiosensitizers and enhanced drug bioavailability over free drug, leading to significant tumor inhibition and improved survival rates under concurrent chemo-radiotherapy. This may due to the sustained drug release, homogenous spatial distribution, and long-term retention ability of IOE in solid PDAC tumor. Furthermore, to better understand the functioning mechanism of drug-loaded IOE, in vitro study is conducted to reveal the ROS- and DNA damage-related therapeutic pathways. Lastly, a comprehensive toxicity assessment also proves the good biocompatibility and safety of as-prepared IOE. This study offers a clinically feasible sensitizer for simultaneous chemoradiotherapy and holds potential for other types of cancer treatment in clinics.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lipiodol emulsion as a dual chemoradiation-sensitizer for pancreatic cancer treatment\",\"authors\":\"\",\"doi\":\"10.1016/j.jconrel.2024.08.020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and limited treatment options. Concurrent chemoradiotherapy is considered beneficial to improve tumor control, but the low drug bioavailability at tumor site and the low radiation tolerance of surrounding healthy organs greatly limits its effectiveness. Lipiodol, a natural drug carrier used in clinical transarterial chemoembolization, has shown potential as a radiosensitizer due to its high Z element iodine composition. Thus, this study aims to repurpose lipiodol as a sensitizer to simultaneously enhance chemo- and radiotherapy for PDAC. To this end, a stable lipiodol emulsion (IOE) loaded with gemcitabine is designed using clinically approved surfactants. At in vivo level, IOE demonstrates better radiotherapeutic effect than existing nanoradiosensitizers and enhanced drug bioavailability over free drug, leading to significant tumor inhibition and improved survival rates under concurrent chemo-radiotherapy. This may due to the sustained drug release, homogenous spatial distribution, and long-term retention ability of IOE in solid PDAC tumor. Furthermore, to better understand the functioning mechanism of drug-loaded IOE, in vitro study is conducted to reveal the ROS- and DNA damage-related therapeutic pathways. Lastly, a comprehensive toxicity assessment also proves the good biocompatibility and safety of as-prepared IOE. This study offers a clinically feasible sensitizer for simultaneous chemoradiotherapy and holds potential for other types of cancer treatment in clinics.</p></div>\",\"PeriodicalId\":15450,\"journal\":{\"name\":\"Journal of Controlled Release\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.5000,\"publicationDate\":\"2024-08-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Controlled Release\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168365924005595\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Controlled Release","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168365924005595","RegionNum":1,"RegionCategory":"医学","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
胰腺导管腺癌(PDAC)生存率低,治疗方案有限。同期化放疗被认为有利于提高肿瘤控制率,但由于肿瘤部位的药物生物利用度低以及周围健康器官的辐射耐受性低,大大限制了其有效性。经动脉化疗栓塞术中使用的天然药物载体 Lipiodol 因其高 Z 元素碘成分而具有放射增敏剂的潜力。因此,本研究旨在重新利用脂碘作为增敏剂,同时加强对 PDAC 的化疗和放疗。为此,我们使用临床认可的表面活性剂设计了一种负载吉西他滨的稳定的脂碘乳剂(IOE)。在体内,IOE 比现有的纳米放射增敏剂具有更好的放射治疗效果,而且比游离药物具有更高的药物生物利用度,从而在同时进行化疗和放疗的情况下显著抑制肿瘤并提高生存率。这可能得益于 IOE 在 PDAC 实体瘤中的持续药物释放、均匀空间分布和长期滞留能力。此外,为了更好地了解药物负载 IOE 的作用机制,还进行了体外研究,以揭示与 ROS 和 DNA 损伤相关的治疗途径。最后,全面的毒性评估也证明了制备的 IOE 具有良好的生物相容性和安全性。这项研究为同步放化疗提供了一种临床上可行的增敏剂,并为临床上其他类型的癌症治疗提供了潜力。
Lipiodol emulsion as a dual chemoradiation-sensitizer for pancreatic cancer treatment
Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and limited treatment options. Concurrent chemoradiotherapy is considered beneficial to improve tumor control, but the low drug bioavailability at tumor site and the low radiation tolerance of surrounding healthy organs greatly limits its effectiveness. Lipiodol, a natural drug carrier used in clinical transarterial chemoembolization, has shown potential as a radiosensitizer due to its high Z element iodine composition. Thus, this study aims to repurpose lipiodol as a sensitizer to simultaneously enhance chemo- and radiotherapy for PDAC. To this end, a stable lipiodol emulsion (IOE) loaded with gemcitabine is designed using clinically approved surfactants. At in vivo level, IOE demonstrates better radiotherapeutic effect than existing nanoradiosensitizers and enhanced drug bioavailability over free drug, leading to significant tumor inhibition and improved survival rates under concurrent chemo-radiotherapy. This may due to the sustained drug release, homogenous spatial distribution, and long-term retention ability of IOE in solid PDAC tumor. Furthermore, to better understand the functioning mechanism of drug-loaded IOE, in vitro study is conducted to reveal the ROS- and DNA damage-related therapeutic pathways. Lastly, a comprehensive toxicity assessment also proves the good biocompatibility and safety of as-prepared IOE. This study offers a clinically feasible sensitizer for simultaneous chemoradiotherapy and holds potential for other types of cancer treatment in clinics.
期刊介绍:
The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System.
Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries.
Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.