Mechanism-Based Sonodynamic-Chemo Combinations against Triple-Negative Breast Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Ultrasound (US)-driven sonodynamic treatment (SDT) offers noninvasive, site-confined irradiation with high tissue penetration for various diseases.
• Inefficient sonosensitizer accumulation at tumor sites limits the effectiveness of SDT.
• Doxorubicin (DOX) induces apoptosis via DNA intercalation, while CHK1 inhibitors like SRA737 target DNA damage response.

Purpose of the Study:

• To develop a deep-penetrating sonochemistry nanoplatform (Pp18-lipos@SRA737&DOX, PSDL) for enhanced ultrasound-activated chemotherapy and SDT.
• To investigate the synergistic effects of SRA737 and DOX delivered via liposomes upon US activation.
• To improve the controlled release of therapeutic agents and reactive oxygen species (ROS) for augmented anticancer effects.

Main Methods:

• Formulation of Pp18 liposomes (Pp18-lipos, Plipo) encapsulating SRA737 and doxorubicin (DOX).
• Characterization of the nanoplatform's deep-penetrating and US-responsive properties.
• In vitro and in vivo evaluation of the nanoplatform's efficacy in breast cancer treatment, assessing cell death, DNA damage, and cell cycle arrest.

Main Results:

• The PSDL nanoplatform demonstrated controlled ROS generation and release of SRA737 and DOX upon US activation.
• SRA737 encapsulated within liposomes alleviated G2/M cell cycle arrest and exacerbated DNA double-strand breaks.
• The combined sono-chemotherapy approach significantly increased cell death and demonstrated potent antitumor activity against breast cancer.

Conclusions:

• The developed US-switchable nanoplatform (PSDL) offers a promising strategy for precise and effective sono-chemotherapy.
• This approach enhances chemotherapeutic effectiveness and boosts SDT efficacy by improving drug delivery and ROS generation.
• The PSDL system provides a controllable and targeted method for augmenting breast cancer treatment.