用于癌症治疗的PD-L1 siRNA纳米载体的最新进展。

Recent advances in PD-L1 siRNA nanocarriers for cancer therapy.

作者信息

Gupta Garima, Abourehab Mohammed A S, Sahebkar Amirhossein, Kesharwani Prashant

机构信息

Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Sector 125, Noida 201301, UP, India.

Graphic Era Hill University, Dehradun 248002, India; School of Allied Medical Sciences, Lovely Professional University, Phagwara, Punjab, India.

出版信息

Int J Biol Macromol. 2025 Jun;311(Pt 3):143994. doi: 10.1016/j.ijbiomac.2025.143994. Epub 2025 May 6.

Abstract

Tumor immune evasion depends on the programmed death-ligand 1 (PD-L1) mechanism, making it a prominent target in cancer therapy. Small interfering RNA (siRNA) designed to inhibit PD-L1 expression presents an innovative approach for boosting immunity against tumors. However, the therapeutic use of siRNA faces challenges, primarily due to its instability and inefficient cellular delivery. Recent advancements in nanocarrier technologies have shown promise in overcoming these obstacles, improving the delivery and efficacy of PD-L1 siRNA. This review comprehensively explores various nanocarrier systems, including lipid nanoparticles, polymeric carriers, and inorganic nanoparticles, highlighting their design innovations and applications in targeting PD-L1 in diverse cancer models. We discuss the synergistic effects of PD-L1 siRNA delivered via nanocarriers in conjunction with chemotherapy and immunomodulators, showcasing their potential to boost immune responses and reduce tumor growth. Additionally, we address ongoing challenges such as optimizing biodistribution and minimizing off-target effects, which hinder clinical translation. By synthesizing recent research findings, this review aims to illuminate the transformative potential of PD-L1 siRNA nanocarriers in cancer immunotherapy, paving the way for future studies aimed at enhancing therapeutic strategies and improving patient outcomes.

摘要

肿瘤免疫逃逸依赖于程序性死亡配体1(PD-L1)机制,使其成为癌症治疗中的一个重要靶点。设计用于抑制PD-L1表达的小干扰RNA(siRNA)为增强抗肿瘤免疫力提供了一种创新方法。然而,siRNA的治疗应用面临挑战,主要是由于其不稳定性和细胞递送效率低下。纳米载体技术的最新进展在克服这些障碍、提高PD-L1 siRNA的递送和疗效方面显示出了前景。本综述全面探讨了各种纳米载体系统,包括脂质纳米颗粒、聚合物载体和无机纳米颗粒,突出了它们在不同癌症模型中靶向PD-L1的设计创新和应用。我们讨论了通过纳米载体递送的PD-L1 siRNA与化疗和免疫调节剂联合使用的协同效应,展示了它们增强免疫反应和减少肿瘤生长的潜力。此外,我们还讨论了诸如优化生物分布和最小化脱靶效应等持续存在的挑战,这些挑战阻碍了临床转化。通过综合近期的研究结果,本综述旨在阐明PD-L1 siRNA纳米载体在癌症免疫治疗中的变革潜力,为未来旨在增强治疗策略和改善患者预后的研究铺平道路。

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