Targeted knockdown: siRNA delivery to lung cancer via mesoporous silica nanoparticles
Maitreyee Mukherjee1, Arnab K Maiti2, Soumen Dhara3
1Bhawanipur Global Campus, Kolkata, 700053, India.
Abstract:
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.
Insights
Mesoporous silica nanoparticles (MSNPs) enhance drug delivery for lung cancer. MSNPs carrying small interfering RNA (siRNA) show promise for overcoming drug resistance and improving treatment efficacy.
Area of Science:
- Biomedical Nanotechnology
- Cancer Therapeutics
- Molecular Oncology
Background:
- Lung cancer presents significant challenges due to metastasis, late diagnosis, and drug resistance.
- While targeted therapies and immunotherapies improve outcomes for specific lung cancer subtypes, intratumoral heterogeneity and acquired resistance limit their long-term effectiveness.
- Conventional hydrophobic chemotherapy drugs suffer from poor solubility and systemic delivery, hindering their therapeutic application.
Purpose of the Study:
- To review the progress of mesoporous silica nanoparticles (MSNPs) in delivering small interfering RNA (siRNA) for lung cancer treatment.
- To examine the barriers associated with siRNA delivery and explore innovative design strategies for MSNPs.
- To highlight the potential of siRNA-MSNP platforms for clinical translation in lung cancer therapy.
Main Methods:
- Review of current literature on MSNPs as nanocarriers for lung cancer therapeutics.
- Analysis of siRNA delivery mechanisms and challenges, including cellular uptake and biodistribution.
- Evaluation of strategies for incorporating siRNA into MSN frameworks to enhance stability and targeting.
Main Results:
- MSNPs effectively enhance the solubility and intravenous delivery of hydrophobic chemotherapeutics.
- MSNPs provide a protective framework for siRNA, improving its stability and cellular uptake.
- Engineered siRNA-MSNP platforms demonstrate potential for selective tumor accumulation and gene silencing in lung cancer models.
Conclusions:
- MSNPs represent a promising nanocarrier system for improving lung cancer treatment by enhancing drug delivery and enabling effective siRNA-based gene silencing.
- Overcoming delivery barriers through strategic MSNPs design is crucial for the clinical translation of siRNA therapeutics.
- The integration of siRNA with MSNPs offers a viable strategy to combat drug resistance and improve therapeutic outcomes in lung cancer.
