Scott G. Tilden , Madison H. Ricco , Emily A. Hemann , Thomas J. Anchordoquy
{"title":"Exploiting a type III interferon response to improve chemotherapeutic safety and efficacy","authors":"Scott G. Tilden , Madison H. Ricco , Emily A. Hemann , Thomas J. Anchordoquy","doi":"10.1016/j.ejps.2024.106974","DOIUrl":null,"url":null,"abstract":"<div><div>Immune reactions to nanomedicines can be detrimental to the patient and compromise efficacy. However, our recent study characterizing the effects of a type III interferon (IFN-λ) response to lipid nanoparticles complexed with nucleic acids (lipoplexes) suggests that an IFN-λ pretreatment can increase tumor accumulation while decreasing off-target distribution of chemotherapeutic nanomedicines. This project provides a direct follow-up to our previously published works by clarifying <strong>1)</strong> which cell type(s) can produce IFN-λ in response to lipoplexes and how the effects of IFN-λ may be propagated in humans. Additionally, we demonstrate <strong>2)</strong> that an IFN-λ pretreatment is also capable of altering the accumulation profile of chemotherapeutic small molecules like doxorubicin. Finally, we determined <strong>3)</strong> that the subcutaneous administration route for an IFN-λ pretreatment is the most efficacious, and <strong>4)</strong> that an IFN-λ pretreatment can significantly increase the survival time of mice receiving Doxil® in a murine CT26 tumor model. With several chemotherapeutic nanomedicines available in the clinic and an IFN-λ product recently completing late phase clinical trials, this study provides the model for a novel anti-cancer treatment regime that can be rapidly translated to the clinic and improve the efficacy of contemporary treatment protocols.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"204 ","pages":"Article 106974"},"PeriodicalIF":4.3000,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0928098724002872","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Immune reactions to nanomedicines can be detrimental to the patient and compromise efficacy. However, our recent study characterizing the effects of a type III interferon (IFN-λ) response to lipid nanoparticles complexed with nucleic acids (lipoplexes) suggests that an IFN-λ pretreatment can increase tumor accumulation while decreasing off-target distribution of chemotherapeutic nanomedicines. This project provides a direct follow-up to our previously published works by clarifying 1) which cell type(s) can produce IFN-λ in response to lipoplexes and how the effects of IFN-λ may be propagated in humans. Additionally, we demonstrate 2) that an IFN-λ pretreatment is also capable of altering the accumulation profile of chemotherapeutic small molecules like doxorubicin. Finally, we determined 3) that the subcutaneous administration route for an IFN-λ pretreatment is the most efficacious, and 4) that an IFN-λ pretreatment can significantly increase the survival time of mice receiving Doxil® in a murine CT26 tumor model. With several chemotherapeutic nanomedicines available in the clinic and an IFN-λ product recently completing late phase clinical trials, this study provides the model for a novel anti-cancer treatment regime that can be rapidly translated to the clinic and improve the efficacy of contemporary treatment protocols.
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