Targeting B7-H3 in Cancer-Associated Fibroblasts Using Nanosystems Suppresses Anaplastic Thyroid Carcinoma...

Area of Science:

• Oncology
• Nanomedicine
• Cancer Biology

Background:

• Anaplastic thyroid carcinoma (ATC) is a rare, aggressive thyroid cancer.
• Cancer-associated fibroblasts (CAFs) promote ATC invasion, migration, and angiogenesis.
• Targeting CAFs offers a potential therapeutic strategy for ATC.

Purpose of the Study:

• To investigate the effects of modulating cancer-associated fibroblasts (CAFs) on anaplastic thyroid carcinoma (ATC) progression.
• To develop and evaluate targeted nanoparticles for B7-H3 knockdown in CAFs.
• To assess the therapeutic potential of targeting B7-H3 in ATC.

Main Methods:

• Development of platelet-derived growth factor receptor (PDGFR-β) targeted polypeptide-modified poly (β-amino ester) (pBAE) nanoparticles carrying siB7-H3 (T-pBAE/siB7-H3 NPs).
• Evaluation of nanoparticle targeting efficacy and B7-H3 gene silencing in CAFs.
• Assessment of the impact of B7-H3 knockdown in CAFs on ATC cell proliferation, invasion, and migration in vitro and in vivo mouse models.

Main Results:

• T-pBAE/siB7-H3 NPs were efficiently internalized by CAFs, achieving targeted B7-H3 knockdown.
• B7-H3 silencing suppressed CAF proliferation and altered cytokine secretion, reducing ATC cell proliferation, invasion, and migration.
• In vivo studies showed reduced tumor volume and downregulation of key markers (PDGFR-β, Ki-67, CD31, CD163, ABCG2) in tumor tissues.

Conclusions:

• PDGFR-β targeted nanoparticles effectively deliver B7-H3 siRNA to CAFs.
• Knockdown of B7-H3 in CAFs inhibits ATC proliferation, invasion, and migration.
• B7-H3 represents a promising therapeutic target for anaplastic thyroid carcinoma.