NANOTECHNOLOGY BASED APPROACHES ON CANCER IMMUNOTHERAPY WITH MIRNA-34 AND LET-7 FAMILY – A REVIEW

Abstract

Background: Dysregulated molecular pathways that enable unchecked growth and immune evasion are the hallmarks of cancer, which continues to be the second most common cause of death worldwide. Although conventional treatments are routine, they often have systemic toxicity and develop multidrug resistance. MicroRNA (miRNA) therapy is a new form of regulation with the application of the miR-34 and let-7 families, which are natural tumor suppressors. Nevertheless, their inability to be absorbed well in their free form and readily degraded by enzymes restrict their therapeutic use.

Purpose: Examine biological functions of miRNA-34 and Let-7 family in the immunotherapy of cancer and in tumor microenvironment reorganization.ng.

 Methodology: Using databases including PubMed, Google Scholar, and Science Direct, a thorough systematic review of the literature was carried out. Peer-reviewed research published between 2015 and 2025 was the main emphasis of the selection criterion. The recent preclinical experiment with nano-formulated miRNA delivery, specific signaling pathways that miR-34 and let-7 activate, and physicochemical properties of nanocarriers were the key areas of discussion.

Findings: The review concludes that nanotechnology is able to re-engineer the pharmacokinetics of miRNA. Important discoveries show that lipid nanoparticles (LNPs) greatly boost cellular absorption through receptor-mediated endocytosis. Moreover, stimuli-responsive nanocarriers reduce off-target effects since they can be released on demand in the acidic tumor microenvironment. The results indicate that let-7 is effective in inhibiting RAS-mediated oncogenic signaling and miR-34 treatment effectively reduces the expression of PD-L1, which in combination lead to a reduction in tumor volume and an increase in T-cell infiltration in preclinical models.

 Conclusion: Delivery of let-7 and miRNA-34 using nanotechnology is essential to achieving their therapeutic success. Such intelligent delivery systems enable immunotherapy to be more precise and efficient by dealing with the issue of endosomal escape and systemic instability. Future studies on the nanotoxicity of nanoparticles should aim to improve standardization of nanotoxicity techniques and address the heterogeneity of tumours to progress these treatments to human clinical trials.