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Updated: Dec 23, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Effect of mesoporous silica nanoparticles co‑loading with 17‑AAG and Torin2 on anaplastic thyroid carcinoma by
Congcong Wang1, Ruiguo Zhang1, Jian Tan1
1Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Abstract:
Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor with a poor prognosis and a low median survival rate because of insufficient effective therapeutic modalities. Recently, mesoporous silica nanoparticles (MSNs) as a green non‑toxic and safe nanomaterial have shown advantages to be a drug carrier and to modify the targeting group to the targeted therapy. To aim of the study was to explore the effects of MSNs co‑loading with 17‑allylamino‑17‑demethoxy‑geldanamycin (17‑AAG; HSP90 inhibitor) and 9‑(6‑aminopyridin‑3‑yl)‑1‑(3‑(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin‑2(1H)‑one (Torin2; mTOR inhibitor) by targeting vascular endothelial growth factor receptor 2 (VEGFR2) on the viability of human anaplastic thyroid carcinoma FRO cells. The cytotoxicity of 17‑AAG and Torin2 were analyzed by MTT assay. The possible synergistic antitumor effects between 17‑AAG and Torin2 were evaluated by CompuSyn software. Flow cytometry was performed to assess the VEGFR2 targeting of (17‑AAG+Torin2)@MSNs‑anti‑VEGFR2 ab and uptake by FRO cells. An ATC xenograft mouse model was established to assess the antitumor effect of (17‑AAG+Torin2)@MSNs‑anti‑VEGFR2 ab in vivo. The results revealed that the combination of 17‑AAG and Torin2 inhibited the growth of FRO cells more effectively compared with single use of these agents. Additionally, the synergistic antitumor effect appeared when concentration ratio of the two drugs was 1:1 along with total drug concentration greater than 0.52 µM. Furthermore, in an ATC animal model, it was revealed that the (17‑AAG+Torin2)@MSNs‑anti‑VEGFR2 ab therapy modality could most effectively prolong the median survival time [39.5 days vs. 33.0 days (non‑targeted) or 27.5 days (control)]. Compared to (17‑AAG+Torin2)@MSNs, the (17‑AAG+Torin2)@MSNs‑anti‑VEGFR2 ab could not only inhibit ATC cell growth but also prolong the median survival time of tumor‑bearing mice in vivo and vitro more effectively, which may provide a new promising therapy for ATC.
Insights
This study shows that combining two drugs, 17-allylamino-17-demethoxy-geldanamycin (17-AAG) and Torin2, loaded onto targeted mesoporous silica nanoparticles (MSNs), effectively inhibits anaplastic thyroid carcinoma (ATC) cell growth and improves survival in mice.
Area of Science:
- Nanomedicine
- Oncology
- Drug Delivery Systems
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive cancer with limited treatment options.
- Mesoporous silica nanoparticles (MSNs) offer a safe and effective platform for targeted drug delivery.
- Targeting vascular endothelial growth factor receptor 2 (VEGFR2) is a potential strategy for ATC treatment.
Purpose of the Study:
- To investigate the efficacy of co-loading 17-allylamino-17-demethoxy-geldanamycin (17-AAG) and Torin2 onto VEGFR2-targeted MSNs for ATC treatment.
- To evaluate the synergistic antitumor effects of 17-AAG and Torin2 in human ATC cells and an ATC xenograft mouse model.
Main Methods:
- Cytotoxicity was assessed using MTT assays.
- Synergistic effects were analyzed using CompuSyn software.
- VEGFR2 targeting and cellular uptake were evaluated by flow cytometry.
- Antitumor effects were assessed in an ATC xenograft mouse model.
Main Results:
- The combination of 17-AAG and Torin2 demonstrated superior inhibition of ATC cell growth compared to individual agents.
- A synergistic antitumor effect was observed at a 1:1 drug ratio and a total concentration >0.52 µM.
- Targeted MSNs co-loaded with 17-AAG and Torin2 significantly prolonged median survival in an ATC mouse model (39.5 days) compared to non-targeted MSNs (33.0 days) and controls (27.5 days).
Conclusions:
- VEGFR2-targeted MSNs co-delivering 17-AAG and Torin2 represent a promising therapeutic strategy for anaplastic thyroid carcinoma.
- This targeted nanomedicine approach enhances antitumor efficacy and survival in preclinical models.
- Further investigation is warranted to explore the clinical potential of this combination therapy for ATC.
