Gene silencing through RNA interference (RNAi), particularly using small double-stranded RNA (siRNA), has been identified as a potent strategy for targeted cancer treatment. Yet, its application faces challenges such as nuclease degradation, inefficient cellular uptake, endosomal entrapment, off-target effects, and immune responses, which have hindered its effective delivery. In the past few years, these challenges have been addressed significantly by using camouflaged metal–organic framework (MOF) nanocarriers. These nanocarriers protect siRNA from degradation, enhance cellular uptake, and reduce unintended side effects by effectively targeting desired cells while evading immune detection. By combining the properties of biomimetic membranes and MOFs, these nanocarriers offer superior benefits such as extended circulation times, enhanced stability, and reduced immune responses. Moreover, through ligand–receptor interactions, biomimetic membrane-coated MOFs achieve homologous targeting, minimizing off-target adverse effects. The MOFs, acting as the core, efficiently encapsulate and protect siRNA molecules, while the biomimetic membrane-coated surface provides homologous targeting, further increasing the precision of siRNA delivery to cancer cells. In particular, the biomimetic membranes help to shield the MOFs from the immune system, avoiding unwanted immune responses and improving their biocompatibility. The combination of siRNA with innovative nanocarriers, such as camouflaged-MOFs, presents a significant advancement in cancer therapy. The ability to deliver siRNA with precision and effectiveness using these camouflaged nanocarriers holds great promise for achieving more personalized and efficient cancer treatments in the future. This review article discusses the significant progress made in the development of siRNA therapeutics for cancer, focusing on their effective delivery through novel nanocarriers, with a particular emphasis on the role of metal–organic frameworks (MOFs) as camouflaged nanocarriers.

中文翻译：

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一种仿生伪装金属有机框架，用于增强肿瘤环境中 siRNA 的递送

通过 RNA 干扰 (RNAi)，特别是使用小双链 RNA (siRNA) 进行基因沉默，已被认为是靶向癌症治疗的有效策略。然而，其应用面临着核酸酶降解、细胞摄取效率低下、内体截留、脱靶效应和免疫反应等挑战，这些都阻碍了其有效递送。在过去几年中，通过使用伪装金属有机框架（MOF）纳米载体，这些挑战得到了显着解决。这些纳米载体可有效靶向所需细胞，同时逃避免疫检测，从而保护 siRNA 免遭降解、增强细胞摄取并减少意外副作用。通过结合仿生膜和 MOF 的特性，这些纳米载体具有卓越的优点，例如延长循环时间、增强稳定性和减少免疫反应。此外，通过配体-受体相互作用，仿生膜涂层 MOF 实现同源靶向，最大限度地减少脱靶副作用。 MOF作为核心，有效封装和保护siRNA分子，而仿生膜包被的表面提供同源靶向，进一步提高了siRNA递送至癌细胞的精度​​。特别是，仿生膜有助于保护 MOF 免受免疫系统的影响，避免不必要的免疫反应并提高其生物相容性。 siRNA 与创新纳米载体（例如伪装 MOF）的结合在癌症治疗方面取得了重大进展。使用这些伪装纳米载体精确有效地递送 siRNA 的能力为未来实现更加个性化和高效的癌症治疗带来了巨大希望。这篇综述文章讨论了 siRNA 癌症疗法开发中取得的重大进展，重点关注其通过新型纳米载体的有效传递，特别强调金属有机框架 (MOF) 作为伪装纳米载体的作用。