X-ray-Responsive Cascade System with Pt/SnO_2-x Heterojunction as Initiators: Fabrication and Investigation for...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Triple-negative breast cancer (TNBC) is characterized by significant resistance to radiotherapy.
• Tumor hypoxia is a major contributor to this radioresistance, limiting treatment efficacy.
• Developing novel strategies to enhance radiosensitivity is crucial for improving TNBC treatment outcomes.

Purpose of the Study:

• To develop an X-ray-responsive cascade system to overcome hypoxia-related radiotherapy resistance in TNBC.
• To investigate the mechanism of action of the cascade system in enhancing radiosensitivity.
• To evaluate the efficacy of the cascade system in vitro and in vivo models of TNBC.

Main Methods:

• Fabrication of a Pt/SnO_2-x@PDA@CaP-GOx cascade system responsive to X-rays.
• In vitro studies using 4T1 cells to assess cell killing rate, DNA damage, and hypoxia alleviation.
• In vivo studies using an in situ transplantation tumor model to evaluate tumor inhibition and volume reduction.

Main Results:

• The X-ray-responsive cascade system effectively alleviated tumor hypoxia and boosted reactive oxygen species (ROS) generation.
• In vitro studies showed an 81% cancer cell killing rate through DNA damage and HIF-1α regulation.
• In vivo studies demonstrated significant inhibition of tumor proliferation, reducing tumor volume to 3% of the original size.

Conclusions:

• The Pt/SnO_2-x@PDA@CaP-GOx cascade system acts as a potent X-ray-responsive radiosensitizer.
• This innovative system offers a promising therapeutic strategy for enhancing triple-negative breast cancer radiotherapy.