Advances in siRNA-Loaded Nanocarriers: Harnessing Cutting-Edge Technologies for Precision Cancer Treatment

Introduction: Cancer remains a major global health concern characterized by the uncontrolled proliferation and spread of abnormal cells. Traditional treatment modalities such as chemotherapy, radiotherapy, and surgery are often associated with limitations, including drug resistance, off-target toxicity, and incomplete eradication of cancer cells. Objective: To explore the potential of small interfering RNA (siRNA)-based therapies in cancer treatment, focusing on their mechanisms of action, delivery challenges, and the application of nanotechnology to enhance therapeutic outcomes. Methods: This review analyzes recent advancements in RNA interference (RNAi) therapy, particularly siRNA- based approaches. It highlights delivery barriers, discusses various nanocarrier systems, including lipidbased, polymeric, and hybrid nanoparticles, and evaluates their roles in improving siRNA stability, intracellular uptake, and tumor-targeting. Results: siRNA offers a highly specific method for silencing disease-related genes at the mRNA level by guiding the RNA-induced silencing complex (RISC) to degrade target transcripts, thereby inhibiting protein synthesis. Despite its therapeutic promise, siRNA delivery faces several challenges including poor stability, limited cellular uptake, and systemic distribution issues. Nanotechnology-based delivery systems have shown significant progress in addressing these barriers and improving therapeutic outcomes in preclinical studies. Discussion: siRNA-based cancer drug delivery provides a targeted and controlled treatment option as an alternative to conventional treatments. As per the literature, the application of nanotechnology improved the stability and efficacy of the aforementioned formulations. The reviewed present various in-depth knowledge about the siRNA-based cancer therapeutics. Conclusion: siRNA-based therapeutics represent a promising strategy for targeted cancer therapy due to their high specificity and ability to reduce off-target toxicity. Nanocarrier systems have greatly enhanced their clinical viability. However, continued efforts are required to overcome biological barriers and facilitate clinical translation. This review also summarizes FDA-approved siRNA-based drugs such as Onpattro®, Leqvio®, Givlaari®, Oxlumo®, Tavnelis®, and Amvuttra®, underscoring the clinical potential of RNAi-based therapies.