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Updated: Dec 3, 2025
Porous Silicon Microparticles for Delivery of siRNA Therapeutics
Published on: January 15, 2015
Rational design of multistage drug delivery vehicles for pulmonary RNA interference therapy
A Sofia Silva1, Kevin E Shopsowitz2, Santiago Correa2
1LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Abstract:
Small interfering RNA (siRNA) therapy has significant potential for the treatment of myriad diseases, including cancer. While intravenous routes of delivery have been found to be effective for efficient targeting to the liver, achieving high accumulations selectively in other organs, including lung tissues, can be a challenge. We demonstrate the rational design and engineering of a layer-by-layer (LbL) nanoparticle-containing aerosol that is able to achieve efficient, multistage delivery of siRNA in vitro. For the purpose, LbL nanoparticles were, for the first time, encapsulated in composite porous micro scale particles using a supercritical CO2-assisted spray drying (SASD) apparatus using chitosan as an excipient. Such particles exhibited aerodynamic properties highly favorable for pulmonary administration, and effective silencing of mutant KRAS in lung cancer cells derived from tumors of a non-small cell lung cancer (NSCLC) autochthonous model. Furthermore, efficient alveolar accumulation following inhalation in healthy mice was also observed, corroborating in vitro aerodynamic results, and opening new perspectives for further studies of effective lung therapies These results show that multistage aerosols assembled by supercritical CO2-assisted spray drying can enable efficient RNA interference therapy of pulmonary diseases including lung cancer.
Insights
This study developed a novel aerosol delivery system for small interfering RNA (siRNA) therapy, enabling efficient RNA interference in lung cancer. The innovative method shows promise for treating pulmonary diseases like non-small cell lung cancer.
Area of Science:
- Biotechnology
- Nanotechnology
- Pulmonary Medicine
Background:
- Small interfering RNA (siRNA) holds therapeutic promise for diseases like cancer.
- Efficient siRNA delivery to lung tissues, beyond the liver, remains a challenge for intravenous methods.
Purpose of the Study:
- To engineer a novel aerosol system for effective, multistage siRNA delivery to lung tissues.
- To evaluate the efficacy of this system in targeting lung cancer cells and achieving alveolar accumulation.
Main Methods:
- Layer-by-layer (LbL) nanoparticles were encapsulated into microparticles using supercritical CO2-assisted spray drying (SASD) with chitosan.
- Aerodynamic properties of the microparticles were assessed for pulmonary administration suitability.
- In vitro silencing of mutant KRAS in non-small cell lung cancer (NSCLC) cells was evaluated.
- In vivo alveolar accumulation in mice following inhalation was investigated.
Main Results:
- The engineered microparticles demonstrated favorable aerodynamic properties for pulmonary delivery.
- Effective silencing of mutant KRAS was achieved in NSCLC cells.
- Significant alveolar accumulation was observed in mice after inhalation, validating in vitro findings.
Conclusions:
- Multistage aerosols assembled via SASD facilitate efficient RNA interference therapy for pulmonary diseases, including lung cancer.
- This approach offers a promising new strategy for developing effective lung-specific siRNA therapies.
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