Small Interfering RNA Carriers for Oncotherapy: A Preclinical Overview.

Introduction: Gene therapy using siRNA is a current area of research in oncology. Although siRNA formulations have not yet been approved for cancer therapy, numerous studies have demonstrated their therapeutic potential for tumor remission. Objective: To provide an overview of the formulations designed and developed to date based on synthetic siRNA for systemic administration to silence cancer genes. Methodology: A thorough search was conducted using the keywords "siRNA", "therapy", and "cancer", with further classification of the resulting works into the various topics addressed in this review. Results: This review encompasses a wide range of aspects, from the design of siRNA using bioinformatics tools to the primary cellular signals and mechanisms targeted for inhibition in cancer therapy. It describes the primary chemical modifications made to siRNA chains to enhance stability, improve bioavailability, and ensure their binding to nanocarrier systems. siRNA formulations ranging from simple conjugates with biomolecules and small molecules to organic, inorganic, and hybrid nanoparticles, which are examined focusing on their advantages and disadvantages. The significance of nanosystems in dual therapy, including siRNA, for developing personalized treatments that achieve better outcomes is emphasized. Conclusions: Personalized cancer therapy appears to be the preferred approach for oncological treatments. To progress, strategies need to be tailored to the patient's genetic profile. siRNA therapies provide a flexible platform for targeting and inhibiting critical oncogenes, enhancing the prospects of genomics-guided, patient-specific therapies.