Bhattacharjee Rahul, Das Debanjan, Chakraborty Srija, Bhaduri Radheka, Chattopadhyay Soham, Singla Rajeev K, Kumarasamy Vinoth, Gundamaraju Rohit
KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India.
St Xavier's College (Autonomous), Kolkata, West Bengal, India.
Int J Biol Sci. 2025 Jul 28;21(11):5116-5134. doi: 10.7150/ijbs.109637. eCollection 2025.
The use of Small interfering RNAs (siRNA) is prevalent in various cancer-based therapies. siRNA is a powerful RNAi, which can be used in clinical oncology with nanoparticles as a vector for delivery. A nano-based siRNA conjugated system has been used to target various multi-drug resistance (MDR) genes of cancer to increase therapeutic specificity and control tumor progression using effective delivery. It offers a targeted avenue in gene silencing with reduced off-target effects. Pre-clinical studies show the effectiveness of this combined siRNA-nanoconjugates therapy in chemotherapeutics resistance to cancer cells. This combinatorial approach not only has the potential to induce an immune response inside the host cells but also renders the MDR genes of various cancers ineffective. The current review focuses on the effect of siRNA entry on immune cells and the factors governing them. Moreover, we have further discussed the limiting factor that controls the siRNA-nanoconjugates efficiency for effective tumor regression. We have enumerated the preclinical and clinical significance of this combined therapy for enhanced tumor regression. Furthermore, we have elaborated the impact of this combined nano-conjugated therapy host immune system while pointing out the limitations posed by them. Thus, in essence, this review provides a unique platform for the readers to understand the potential of siRNA-conjugates for anti-cancer therapy from pre-clinical to bench side.
小干扰RNA（siRNA）在各种基于癌症的治疗中广泛应用。siRNA是一种强大的RNA干扰技术，可与纳米颗粒作为载体用于临床肿瘤学。基于纳米的siRNA共轭系统已被用于靶向癌症的各种多药耐药（MDR）基因，以提高治疗特异性并通过有效递送控制肿瘤进展。它为基因沉默提供了一条靶向途径，减少脱靶效应。临床前研究表明这种联合的siRNA-纳米共轭物疗法对癌细胞化疗耐药的有效性。这种联合方法不仅有可能在宿主细胞内诱导免疫反应，还能使各种癌症的MDR基因失效。当前的综述重点关注siRNA进入免疫细胞的影响及其调控因素。此外，我们进一步讨论了控制siRNA-纳米共轭物有效肿瘤消退效率的限制因素。我们列举了这种联合疗法对增强肿瘤消退的临床前和临床意义。此外，我们阐述了这种联合纳米共轭疗法对宿主免疫系统的影响，同时指出了它们带来的局限性。因此，本质上，本综述为读者提供了一个独特的平台，以了解从临床前到床边的siRNA共轭物在抗癌治疗中的潜力。
