Combined miR-181a-5p and Ag Nanoparticles are Effective Against Oral Cancer in a Mouse Model

Guoqiang Xu1,2, Xiaona Song2, Xiaotang Wang1,2

  • 1Laboratory Animal Center Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Taiyuan, People's Republic of China.

PubMed
Abstract

Insights

Nanosilver particles loaded with miR-181a-5p effectively inhibit oral cancer growth and metastasis. This novel combination therapy targets the β-catenin pathway, offering a promising new treatment for oral squamous cell carcinoma.

Area of Science:

  • Nanotechnology
  • Molecular Biology
  • Oncology

Background:

  • Oral squamous cell carcinoma (OSCC) presents high metastasis and recurrence rates, with limited therapeutic advancements.
  • MicroRNA (miRNA) therapies show potential for cancer gene therapy but face challenges in oral cancer treatment.
  • Nanotechnology-based drug delivery systems offer enhanced efficacy for oral cancer treatment.

Purpose of the Study:

  • To synthesize and characterize nanosilver particles (AgNPs) loaded with the tumor suppressor miR-181a-5p.
  • To evaluate the in vitro and in vivo anti-cancer effects of the miR-181a-5p/AgNPs nanocomposites on oral cancer.
  • To elucidate the molecular mechanisms underlying the therapeutic effects of the nanocomposites.

Main Methods:

  • Synthesis of spherical AgNPs (50-100 nm) with green fluorescence.
  • Loading of AgNPs with miR-181a-5p to protect it from degradation.
  • In vitro assessment of nanocomposite effects on oral cancer cell proliferation, invasion, migration, and colony formation.
  • In vivo xenograft studies to evaluate tumor growth suppression and molecular pathway involvement.

Main Results:

  • AgNPs effectively protected loaded miR-181a-5p from degradation.
  • The miR-181a-5p/AgNPs nanocomposites significantly inhibited oral cancer cell malignant behaviors in vitro.
  • Substantial tumor growth suppression was observed in vivo, with direct targeting of BCL2 and suppression of the β-catenin signaling pathway.
  • No acute toxicity was observed in the xenograft model.

Conclusions:

  • The miR-181a-5p/AgNPs combination demonstrates significant efficacy in impeding oral cancer growth and progression both in vitro and in vivo.
  • The β-catenin signaling pathway plays a pivotal role in the observed anti-tumor effects.
  • This nanotechnology-based miRNA delivery system represents a promising therapeutic strategy for oral cancer management.