Precision engineering of macrophage reprogramming with RNA interference-loaded lipid nanoparticles: a game-changer in cancer immunotherapy.

IF 5.5 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Sezen Gül, Juliette Vergnaud, François Fay, Elias Fattal
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Abstract

Tumor-associated macrophages (TAMs) represent solid tumors' most prevalent immune cell subset. These cells primarily adopt an immunosuppressive phenotype in the tumor microenvironment, promoting tumor initiation and progression. Their ability to shift between distinct activation states identifies TAMs as ideal targets for cancer treatment. Consequently, reprogramming TAMs from an immunosuppressive to an immunostimulatory state has emerged as a promising therapeutic approach to fight cancer. RNA interference has gained significant attention as a therapeutic modality due to its potential to selectively inhibit the expression of one or several critical proteins for the pro-tumorous activities of TAMs. However, the efficiency of RNA interference is limited by its susceptibility to nuclease degradation, rapid clearance from the body, and poor cellular uptake. These limitations necessitate the development of delivery systems to enhance their therapeutic potential. Among the nanocarriers we discuss in this review, lipid nanoparticles (LNPs) have been widely recognized as the most effective for siRNA or miRNA, providing stability, high gene silencing efficiency, and biocompatibility. The clinical application of LNPs has been further advanced by recent progress in microfluidics, enabling reproducible and scalable production of LNPs with high encapsulation efficiency. The increasing number of preclinical studies shows the growing interest in cancer immunotherapy using RNA interference-LNPs. In this review, we summarize the current knowledge on macrophage biology and its role in cancer, explore advancements in RNA interference-LNP technology, review ongoing research efforts, and discuss key translational challenges that must be addressed for the clinical success of RNA interference-LNP-based macrophage reprogramming.

负载RNA干扰的脂质纳米颗粒巨噬细胞重编程的精密工程:癌症免疫治疗的游戏规则改变者。
肿瘤相关巨噬细胞(tam)代表实体肿瘤中最普遍的免疫细胞亚群。这些细胞在肿瘤微环境中主要采用免疫抑制表型,促进肿瘤的发生和发展。它们在不同激活状态之间转换的能力使tam成为癌症治疗的理想靶点。因此,将tam从免疫抑制状态重编程为免疫刺激状态已成为对抗癌症的一种有前途的治疗方法。RNA干扰作为一种治疗方式受到了极大的关注,因为它有可能选择性地抑制tam促肿瘤活性的一种或几种关键蛋白的表达。然而,RNA干扰的效率受到其对核酸酶降解的易感性、从体内快速清除和细胞摄取不良的限制。这些限制需要发展输送系统以增强其治疗潜力。在我们讨论的纳米载体中,脂质纳米颗粒(LNPs)被广泛认为是siRNA或miRNA最有效的载体,具有稳定性、高基因沉默效率和生物相容性。近年来,微流体技术的发展进一步推动了LNPs的临床应用,使LNPs具有高封装效率,可重复性和可扩展的生产成为可能。越来越多的临床前研究表明,利用RNA干扰- lnps进行癌症免疫治疗的兴趣日益浓厚。在这篇综述中,我们总结了目前巨噬细胞生物学及其在癌症中的作用,探讨了RNA干扰- lnp技术的进展,回顾了正在进行的研究工作,并讨论了基于RNA干扰- lnp的巨噬细胞重编程临床成功必须解决的关键翻译挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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