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Article Abstract
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 and CD8 T cells and potentiate T-cell-mediated adaptive immune response. Our work provides an MT 2A-silencing nanoagonist for highly effective combination therapy and metastasis inhibition of gynecologic malignancies.
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| http://dx.doi.org/10.1021/acsnano.5c07692 | DOI Listing |
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