Metallothionein 2A-Silencing Antimonene-Based Nanoagonist for Amplifying the Photothermal Immunotherapy of Gynecologic Malignancy
Gynecologic malignancies are prone to metastasis and recurrence due to the low efficacy and sensitivity of current clinical treatments. Here, we construct ultrasmall Sb@Au nanodots (Sb@Au NDs) as a metallothionein 2A (MT 2A)-silencing nanoagonist for effective photothermal immunotherapy of gynecologic malignancies. Sb@Au NDs show high photothermal conversion efficiency of 56.8% under a 1270 nm laser and exceptional capability for downregulating MT 2A overexpressed in gynecologic malignancies. Synergizing mild photothermal therapy (PTT) with targeting downregulation of MT 2A based on Sb@Au NDs offers a robust therapeutic effect, significantly activating adaptive immune response and inhibiting the metastasis of gynecologic malignancies. RNA sequencing results of SKOV-3 cells elucidate that MT 2A downregulation by Sb@Au NDs impedes the transcription of zinc finger protein genes, thereby triggering the TGF-β signaling pathway, which blocks the cell cycle and activates the MAPK/c-fos apoptotic pathway to sensitize the treatment of gynecologic malignancies. Mild PTT synergizing with MT 2A downregulation by Sb@Au NDs can promote the secretion of β-defensin to increase the infiltration of CD4
Journal
ACS NanoInstitutions
Authors
Funding
Natural Science Research of Jiangsu Higher Education Institutions of China Grant 22KJA430007Natural Science Foundation of Jiangsu Province Grant BK20212012Natural Science Foundation of Jiangsu Province Grant BK20240648National Natural Science Foundation of China Grant 22275096National Natural Science Foundation of China Grant 62227803National Natural Science Foundation of China Grant 62288102National Natural Science Foundation of China Grant 82404567