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Co-delivery Of Il-12 Mrna And Small-molecule Prodrug With Lung-tropic Lipid Nanoparticles For Synergistic Cancer Therapy.

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Co-delivery Of Il-12 Mrna And Small-molecule Prodrug With Lung-tropic Lipid Nanoparticles For Synergistic Cancer Therapy.

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Co-delivery of IL-12 mRNA and small-molecule prodrug with lung-tropic lipid nanoparticles for synergistic cancer

Jiahui Jin¹, Xiaoyi Liu¹, Guofeng Zhu¹

¹School of Medicine, Southern University of Science and Technology, Shenzhen 518055, PR China.

International Journal of Pharmaceutics

|June 12, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Researchers developed a novel lung-tropic lipid nanoparticle (LNP) platform for delivering interleukin-12 (IL-12) mRNA and docetaxel to treat lung cancer. This combination therapy effectively reduced tumors in mice without significant toxicity, offering a promising strategy for metastatic lung disease.

Keywords:

Docetaxel Prodrug IL-12 mRNA Lipid Nanoparticles Lung-Targeted

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Area of Science:

Biotechnology
Nanomedicine
Oncology

Background:

Messenger RNA (mRNA) therapeutics show promise but face challenges in targeted delivery to tissues outside the liver.
Lung metastasis is a significant clinical problem requiring effective therapeutic strategies.

Purpose of the Study:

To engineer a lung-tropic lipid nanoparticle (LNP) platform for co-delivery of interleukin-12 (IL-12) mRNA and docetaxel prodrug.
To evaluate the efficacy and safety of this combination therapy in a preclinical lung metastasis model.

Main Methods:

Optimization of synthetic cationic lipids to identify N112 as the lead candidate for lung-tropic LNPs.
Formulation of N112-DOTAP LNPs for co-encapsulation of IL-12 mRNA and docetaxel prodrug.
Assessment of transfection efficiency, particle characteristics, and antitumor efficacy in a B16F10 lung metastasis mouse model.

Main Results:

The N112-DOTAP LNP formulation exhibited enhanced transfection efficiency in lung tissue compared to a benchmark MC3-DOTAP LNP.
LNPs demonstrated uniform particle size and high encapsulation efficiency for both mRNA and docetaxel.
Combination therapy significantly reduced lung tumor nodules and demonstrated a favorable safety profile with no significant body weight loss or organ toxicity.

Conclusions:

A novel lung-tropic LNP platform enables efficient co-delivery of IL-12 mRNA and docetaxel for treating lung metastasis.
This mRNA-based combination therapy offers a potent and safe strategy against lung metastatic disease.
The developed LNP platform holds potential for advancing mRNA-based cancer therapeutics.