ROS Generative Black Phosphorus-Tamoxifen Nanosheets for Targeted Endocrine-Sonodynamic Synergistic Breast Cancer...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Oncology

Background:

• Tamoxifen (TAM) is crucial for estrogen receptor-positive (ER+) breast cancer but faces challenges like low bioavailability and resistance.
• Developing novel drug delivery systems is essential to overcome TAM limitations and improve therapeutic efficacy.

Purpose of the Study:

• To create a black phosphorus (BP)-based nanoplatform (TAM@BP-FA) for synergistic endocrine and sonodynamic therapy (SDT) of breast cancer.
• To evaluate the efficacy and mechanisms of TAM@BP-FA in TAM-sensitive and TAM-resistant breast cancer models.

Main Methods:

• Fabrication of TAM@BP-FA by modifying BP nanosheets with dopamine, then adsorbing TAM and folic acid (FA).
• In vitro and in vivo evaluation of anticancer effects, including cytotoxicity, drug release, and ROS generation.
• Mechanism investigation using RNA-sequencing, PCR, Western blot, flow cytometry, and PBMC analysis.

Main Results:

• TAM@BP-FA demonstrated controlled TAM release, efficient ROS generation under ultrasound, and enhanced cellular uptake.
• The nanoplatform showed superior antitumor efficacy in TAM-resistant cells compared to TAM alone, with SDT further increasing cell death.
• TAM@BP-FA modulated immune responses by upregulating NK cells and reducing immunosuppressive macrophages.

Conclusions:

• The novel BP-based nanoplatform offers targeted delivery of TAM and synergistic effects via endocrine therapy, SDT, and immune modulation.
• TAM@BP-FA presents a promising strategy for overcoming TAM resistance and enhancing breast cancer treatment.