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Published on: December 1, 2016
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.
Purpose:
Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.
Methods:
We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.
Results:
The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.
Conclusion:
Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.
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.

