{"title":"SN-38-indoximod conjugate: carrier free nano-prodrug for cancer therapy.","authors":"Sanjay Kumar, Yoshitaka Koseki, Keita Tanita, Aki Shibata, Asuka Mizutani, Hitoshi Kasai","doi":"10.1080/20415990.2025.2458449","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The integration of immunotherapy alongside chemotherapy represents a crucial approach in the treatment of cancer. Herein we report the SN-38-indoximod conjugate nano-prodrug to address the difficulties encountered by individuals. In this prodrug, SN-38 is connected to indoximod through a specific disulfide linker, which enables the release of the components in response to the tumor microenvironment characterized by elevated levels of glutathione, thereby facilitating programmed chemoimmunotherapy.</p><p><strong>Results: </strong>SN-38-indoximod conjugate was synthesized and fabricated to nano-prodrug by reprecipitation method. It showed comparable anti-cancer activity against A549 cells than SN-38 (IC<sub>50</sub> = 0.24 ± 0.01 µM) with IC<sub>50</sub> value 0.32 ± 0.04 µM. It inhibited 90% A549 cell at very lower concentration (IC<sub>90</sub> = 6.07 ± 0.41 µM) as compared with SN-38 (IC<sub>90</sub> = 24.60 ± 1.24 µM) and mixture of SN-38: indoximod (1:1, IC<sub>90</sub> >30 µM). The nano-prodrug showed better size distribution profile and dispersion stability contains nanoparticles in effective size range (80-160 nm) required for the EPR effect.</p><p><strong>Conclusion: </strong>This research offers valuable insights into the advancement of conjugate nano-prodrugs exhibiting synergistic pharmacological effects, while also presenting novel opportunities for the design of prodrug molecules capable of releasing drugs in response to diverse triggers.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":" ","pages":"217-226"},"PeriodicalIF":3.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875466/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic delivery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/20415990.2025.2458449","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/31 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The integration of immunotherapy alongside chemotherapy represents a crucial approach in the treatment of cancer. Herein we report the SN-38-indoximod conjugate nano-prodrug to address the difficulties encountered by individuals. In this prodrug, SN-38 is connected to indoximod through a specific disulfide linker, which enables the release of the components in response to the tumor microenvironment characterized by elevated levels of glutathione, thereby facilitating programmed chemoimmunotherapy.
Results: SN-38-indoximod conjugate was synthesized and fabricated to nano-prodrug by reprecipitation method. It showed comparable anti-cancer activity against A549 cells than SN-38 (IC50 = 0.24 ± 0.01 µM) with IC50 value 0.32 ± 0.04 µM. It inhibited 90% A549 cell at very lower concentration (IC90 = 6.07 ± 0.41 µM) as compared with SN-38 (IC90 = 24.60 ± 1.24 µM) and mixture of SN-38: indoximod (1:1, IC90 >30 µM). The nano-prodrug showed better size distribution profile and dispersion stability contains nanoparticles in effective size range (80-160 nm) required for the EPR effect.
Conclusion: This research offers valuable insights into the advancement of conjugate nano-prodrugs exhibiting synergistic pharmacological effects, while also presenting novel opportunities for the design of prodrug molecules capable of releasing drugs in response to diverse triggers.
期刊介绍：
Delivering therapeutics in a way that is right for the patient - safe, painless, reliable, targeted, efficient and cost effective - is the fundamental aim of scientists working in this area. Correspondingly, this evolving field has already yielded a diversity of delivery methods, including injectors, controlled release formulations, drug eluting implants and transdermal patches. Rapid technological advances and the desire to improve the efficacy and safety profile of existing medications by specific targeting to the site of action, combined with the drive to improve patient compliance, continue to fuel rapid research progress. Furthermore, the emergence of cell-based therapeutics and biopharmaceuticals such as proteins, peptides and nucleotides presents scientists with new and exciting challenges for the application of therapeutic delivery science and technology. Successful delivery strategies increasingly rely upon collaboration across a diversity of fields, including biology, chemistry, pharmacology, nanotechnology, physiology, materials science and engineering. Therapeutic Delivery recognizes the importance of this diverse research platform and encourages the publication of articles that reflect the highly interdisciplinary nature of the field. In a highly competitive industry, Therapeutic Delivery provides the busy researcher with a forum for the rapid publication of original research and critical reviews of all the latest relevant and significant developments, and focuses on how the technological, pharmacological, clinical and physiological aspects come together to successfully deliver modern therapeutics to patients. The journal delivers this essential information in concise, at-a-glance article formats that are readily accessible to the full spectrum of therapeutic delivery researchers.
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