Targeted knockdown: siRNA delivery to lung cancer via mesoporous silica nanoparticles.

Among all the cancers, lung cancer remains the foremost clinical challenge due to its metastatic progression, late-stage diagnosis, and the persistent emergence of drug resistance. While recent advances in precise targeted therapies and immune checkpoint inhibitors have augmented outcomes for genetically defined subcategories of non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), their enduring effectiveness is often inhibited by intratumoral heterogeneity and acquired resistance. Traditional chemotherapeutics frequently used for lung cancer management are chiefly hydrophobic, limiting solubility and systemic delivery. Mesoporous silica nanoparticles (MSNPs) have therefore gained eminence as robust nanocarriers capable of enhancing the aqueous solubility and intravenous delivery of such therapeutics. Parallel to these advances, small interfering RNA (siRNA) has appeared as a powerful modality for gene-specific silencing of cancer gene concerned with lung tumour development and therapy resistance. Yet, the therapeutic translation of siRNA is stalled by rapid, poor cellular uptake, enzymatic degradation, and nonspecific biodistribution. Incorporating siRNA into MSN frameworks offers a promising approach to improve intracellular transport by protecting siRNA and achieving selective tumour accumulation. This review collates current progress in MSN-mediated siRNA delivery for lung cancer, examines delivery barriers and emerging design strategies, and highlights prospects for developing clinically translatable siRNA-MSNP platforms, hinting at the adapted pathways.