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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
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RNA-Loaded Nanoparticles for Targeted Lung Delivery.

Mark John Siringan1, Xiaoyang Chen1, Jiawei Huo1,2

  • 1Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Biomedicines
|May 27, 2026
PubMed
Summary

Pulmonary RNA therapeutics face delivery challenges due to biological barriers. Nanoparticle systems protect RNA and improve lung delivery, paving the way for new treatments.

Keywords:
RNA therapeuticslung cancerlung targetingnanoparticle delivery

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Area of Science:

  • Pulmonary drug delivery and nanomedicine.

Background:

  • The lungs offer a large, accessible surface for RNA therapeutics via inhalation.
  • Efficient delivery of RNA (siRNA, miRNA, mRNA, CRISPR-Cas) to the lungs is hindered by biological barriers like mucus, immune responses, and poor cellular uptake.
  • Aerosolization can damage RNA, further complicating delivery.

Purpose of the Study:

  • To review biological barriers to lung-targeted RNA delivery.
  • To highlight nanoparticle-based strategies for overcoming these barriers.
  • To discuss design principles and clinical potential of RNA-loaded nanoparticles for pulmonary diseases.

Main Methods:

  • Examination of biological barriers affecting pulmonary RNA delivery.
  • Review of nanoparticle systems (lipid, polymeric, inorganic) for RNA protection and delivery.
  • Analysis of RNA stability, transport, and release mechanisms.
  • Comparison of nanoparticle platform strengths, limitations, and clinical readiness.

Main Results:

  • Nanoparticles protect RNA cargo, enhance mucus penetration, and improve cellular uptake for effective pulmonary delivery.
  • Various nanoparticle platforms show promise, each with unique advantages and disadvantages regarding toxicity, biodegradability, and clinical translation.
  • Lung cancer is presented as a model for emerging clinical applications of RNA-loaded nanoparticles.

Conclusions:

  • Nanoparticle engineering is crucial for overcoming pulmonary delivery challenges for RNA therapeutics.
  • Continued innovation in nanoparticle design and delivery strategies will accelerate the clinical translation of RNA-based lung treatments.
  • Addressing toxicity, biodegradability, and clinical readiness is essential for successful translation.