Related Experiment Video

Updated: Mar 18, 2026

Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy
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Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy

Published on: June 21, 2013

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Cytidinyl/Cationic Lipids-siRNA Delivery Silences MYC to Reprogram Macrophages and Circadian Rhythm for Cancer

Xinyang Zhou1,2, Xiaotong Yu3, Kaidi Qiu2

  • 1School of Criminal Investigation, People's Public Security University of China, Beijing 100038, China.

Molecular Pharmaceutics
|March 17, 2026
PubMed

Insights

Researchers developed a novel nanoparticle delivery system for silencing the MYC oncogene in nonsmall cell lung cancer (NSCLC). This approach effectively inhibits tumor growth, reshapes the immune microenvironment, and restores circadian rhythm.

Area of Science:

  • Oncology
  • Nanotechnology
  • Immunology
  • Molecular Biology

Background:

  • Nonsmall cell lung cancer (NSCLC) is a major cause of cancer mortality.
  • Overexpression of the MYC oncogene drives NSCLC progression and immune suppression.
  • MYC has been considered 'undruggable', with its impact on macrophage polarization and circadian rhythm unexplored.

Purpose of the Study:

  • To develop an efficient delivery system for MYC siRNA.
  • To investigate the effects of MYC silencing on tumor immunity and circadian rhythm in NSCLC.

Main Methods:

  • Development of a lipid nanoparticle (siMYC@Dmix) for MYC siRNA delivery, comprising DNCA, CLD, and DSPE-PEG2000.
  • In vitro assessment of cellular uptake, lysosomal escape, and MYC mRNA silencing in Lewis Lung Carcinoma (LLC) cells.
  • In vivo evaluation of tumor growth inhibition, immune microenvironment modulation, and circadian gene expression in C57BL/6J mice.

Main Results:

  • siMYC@Dmix demonstrated efficient MYC mRNA silencing (∼77%) in LLC cells.
  • In vivo treatment significantly inhibited tumor growth and remodeled the tumor immune microenvironment.
  • Macrophage polarization shifted to M1 phenotype, CD8+ T cell and NK cell activity increased, and dendritic cell maturation was enhanced.
  • MYC silencing restored the expression of core circadian clock genes.

Conclusions:

  • The developed siMYC@Dmix nanoparticle is a promising RNAi-based strategy for NSCLC.
  • MYC silencing concurrently targets tumorigenesis, corrects circadian dysfunction, and reinstates antitumor immunity.
  • This approach offers a multifaceted therapeutic strategy for NSCLC.
Keywords:
MYC silencingcancer therapycircadian clockcytidinyl lipidtumor immune microenvironment

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