Nanoformulations Downregulating METTL16 Combined with mRNA Tumor Vaccines Suppress Triple-Negative Breast Cancer and

Runying Wang1, Yufeng Zhang1, Shubo Du1

  • 1MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, 116024, People's Republic of China.

Abstract

Insights

This study developed a novel nanoformulation to silence METTL16, effectively inhibiting triple-negative breast cancer (TNBC) growth and metastasis when combined with mRNA tumor vaccines.

Area of Science:

  • Biomedical Engineering
  • Oncology
  • Nanotechnology

Background:

  • Triple-negative breast cancer (TNBC) is highly aggressive with limited treatment options.
  • METTL16 has been identified as a potential therapeutic target for TNBC.
  • Current treatments for TNBC are insufficient to address its malignancy and recurrence.

Purpose of the Study:

  • To develop a nanoformulation for silencing METTL16 in TNBC.
  • To evaluate the combined efficacy of the nanoformulation and mRNA tumor vaccines against TNBC.
  • To inhibit TNBC growth, malignancy, and metastasis.

Main Methods:

  • Microfluidic technology was used for efficient siRNA encapsulation in lipid nanoparticles (LNPs).
  • Developed LNP/siMETTL16 and selective organ-targeting LNP/siMETTL16 (SORT-LNP/siMETTL16).
  • Evaluated antitumor properties in cellular and mouse TNBC models, including subcutaneous tumors and lung metastasis.

Main Results:

  • LNP/siMETTL16 demonstrated efficient silencing of METTL16 and inhibited tumor cell activity.
  • Combination therapy of LNP/siMETTL16 and LNP/mMUC1 suppressed subcutaneous tumor growth by 66.0%.
  • Combined SORT-LNP/siMETTL16 and mRNA tumor vaccines significantly alleviated TNBC lung metastasis.

Conclusions:

  • METTL16 is a viable therapeutic target for TNBC.
  • The developed nanoformulation offers a novel strategy for combined treatment of TNBC.
  • This approach shows promise for clinical translation in TNBC therapy.

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