PTFTH Nanoplatform for TNBC Therapy

Triple-negative breast cancer (TNBC) carries one of the worst prognoses among breast cancer subtypes and urgently requires effective treatment methods. Cancer’s complex nature often necessitates multiple treatment modalities for effective management.

Yuhang Tian and the team aimed to construct a TME-responsive PFC/TRIM37@Fe-TA@HA (PTFTH) nanoplatform to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro.

The PTFTH nanoplatform was constructed by coating Fe3⁺and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA). The design aimed to facilitate tumor-specific delivery and internalisation into tumor cells through CD44 receptor-mediated active targeting.

The PTFTH nanoplatform exhibited good biocompatibility in vitro. The released Fe3⁺ depleted overexpressed glutathione (GSH) and produced Fe2⁺, generating cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). Local hyperthermia induced by PTFTH under 808 nm laser irradiation enhanced CDT efficacy and TRIM37-siRNA delivery for gene therapy.

Synergistic effects of GSH consumption and •OH accumulation led to substantial tumor cell ferroptosis. Additionally, PTFTH demonstrated excellent contrast-enhanced ultrasound (CEUS), photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capabilities.

The PTFTH-based multiple-mode therapeutic strategy successfully achieved a synergistic anticancer effect in vitro, indicating its potential for translation into clinical application for tumor therapy.

No funding information was available.

Source: https://pubmed.ncbi.nlm.nih.gov/39258005/

Tian Y, He X, Yuan Y, et al. (2024). “TME-Responsive Nanoplatform with Glutathione Depletion for Enhanced Tumor-Specific Mild Photothermal/Gene/Ferroptosis Synergistic Therapy. Int J Nanomedicine.” 2024;19:9145-9160. Published 2024 Sep 6. doi:10.2147/IJN.S475698