Precision RNA-based Gene Silencing and Theranostics Delivery Strategies for Glioma: Advances in siRNA and Emerging miRNA Therapeutics.

INTRODUCTION Gliomas, particularly Glioblastoma Multiforme (GBM), remain highly lethal despite surgery, radiotherapy, and chemotherapy, largely due to their infiltrative biology, marked molecular heterogeneity, and the restrictive Blood-Brain Barrier. RNA interference (RNAi)-based therapeutics, including Small Interfering RNA (siRNA) and emerging microRNA (miRNA)-modulating strategies, enable targeted silencing of oncogenic drivers. However, their clinical application is constrained by rapid systemic clearance, nuclease-mediated degradation, off-target effects, and inefficient brain delivery.

Objective

This review evaluates recent advances in RNA-based precision gene silencing for glioma, with particular focus on siRNA therapeutics, emerging miRNA strategies, nanocarrier-enabled delivery systems, and theranostic integration for imaging-guided therapy.

Method

A comprehensive literature search (1998-2026) of PubMed, Scopus, and Google Scholar was performed to identify preclinical and early clinical studies addressing glioma pathobiology, RNA interference mechanisms, siRNA targets, nanocarrier platforms, and imaging-guided theranostic systems, with emphasis on orthotopic models, registered clinical trials, and mechanistically well-characterized datasets.

Results

Non-viral nanocarriers (lipid nanoparticles, bio-reducible polymers, dendrimer-gold, exosomes) enable siRNA protection, BBB penetration, and knockdown of EGFR, STAT3, BCL-2, VEGF, and GLUT-3 in orthotopic glioma models. Emerging miRNA-based strategies, including anti-miR-21 and miR-100 modulation, showed potential for reversing chemoresistance. Combination therapies with temozolomide/doxorubicin produced greater efficacy than single-agent approaches. Theranostic imaging platforms (PET/MRI/SPECT) enabled real-time monitoring of biodistribution and treatment responses.

Conclusion

RNA-based theranostic strategies show promising potential for glioma therapy. However, further optimization of delivery systems, improved safety profiles, and successful clinical translation remain necessary.