{"title":"Multifunctional delivery strategies and nanoplatforms of SN-38 in cancer therapeutics","authors":"Mercedes Lozano-García, Emre Dikici, Daniel Bilbao, Prasoon Mohan, Sapna Deo, Sylvia Daunert","doi":"10.1016/j.jconrel.2025.113937","DOIUrl":null,"url":null,"abstract":"SN-38 or 7-ethyl-10-hydroxycamptothecin is the active metabolite of irinotecan, a widely used chemotherapeutic agent for the treatment of colorectal, pancreatic, lung, breast, gastric, esophageal, hepatocellular, ovarian, brain, leukemia, and lymphoma malignancies. SN-38's antitumoral effect is 100 to 1000 times more potent than that of irinotecan. However, its clinical application is hindered by its poor solubility and chemical instability. To circumvent these challenges and avoid systemic toxicities, such as myelosuppression and diarrhea, several SN-38 delivery systems have been explored. In that regard, formulations based on targeted, controlled and tumor-responsive release of SN-38 have demonstrated to enhance its antitumoral effects and reduce the associated systemic toxicities by limiting the pharmacological activity to the desired tumor location. To this end, prodrugs, conjugates, nanoparticles, dendrimers, or lipid-based strategies for SN-38 delivery have been used. Most recently, multifunctional approaches have emerged as an attractive alternative to develop SN-38 delivery systems, combining several strategies in a single formulation, <em>i.e.</em>, encapsulating nanocarriers, tumor-targeting ligands, stimuli-responsive elements, optimal linkers, drug combinations or bioimaging agents. Despite their therapeutic advantages, multifunctional delivery systems often face challenges concerning their clinical translation compared to conventional therapies, such as biocompatibility, scalability and cost-effectiveness issues. The aim of this work is to review the most recent progress that has been made in the development and assessment of multifunctional delivery systems for cancer treatment.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"14 1","pages":""},"PeriodicalIF":10.5000,"publicationDate":"2025-06-07","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://doi.org/10.1016/j.jconrel.2025.113937","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
Abstract
SN-38 or 7-ethyl-10-hydroxycamptothecin is the active metabolite of irinotecan, a widely used chemotherapeutic agent for the treatment of colorectal, pancreatic, lung, breast, gastric, esophageal, hepatocellular, ovarian, brain, leukemia, and lymphoma malignancies. SN-38's antitumoral effect is 100 to 1000 times more potent than that of irinotecan. However, its clinical application is hindered by its poor solubility and chemical instability. To circumvent these challenges and avoid systemic toxicities, such as myelosuppression and diarrhea, several SN-38 delivery systems have been explored. In that regard, formulations based on targeted, controlled and tumor-responsive release of SN-38 have demonstrated to enhance its antitumoral effects and reduce the associated systemic toxicities by limiting the pharmacological activity to the desired tumor location. To this end, prodrugs, conjugates, nanoparticles, dendrimers, or lipid-based strategies for SN-38 delivery have been used. Most recently, multifunctional approaches have emerged as an attractive alternative to develop SN-38 delivery systems, combining several strategies in a single formulation, i.e., encapsulating nanocarriers, tumor-targeting ligands, stimuli-responsive elements, optimal linkers, drug combinations or bioimaging agents. Despite their therapeutic advantages, multifunctional delivery systems often face challenges concerning their clinical translation compared to conventional therapies, such as biocompatibility, scalability and cost-effectiveness issues. The aim of this work is to review the most recent progress that has been made in the development and assessment of multifunctional delivery systems for cancer treatment.
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.