Self-Activated Cascade-Tailored Small Molecule for Cancer Therapy, Companion Diagnostics, and "Theranostic...

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Cancer Therapy

Background:

• Companion diagnostics (CDx) are vital for personalized medicine but often limited to in vitro use.
• Current methods struggle to assess real-time drug efficacy and account for tumor heterogeneity in vivo.
• There is a need for integrated diagnostic and therapeutic tools for effective cancer treatment monitoring.

Purpose of the Study:

• To develop a novel cascade-responsive small molecule, Cbl-DEVD-Hcy, for simultaneous cancer therapy and in vivo treatment evaluation.
• To enable real-time monitoring of therapeutic response and tumor apoptosis.
• To establish a theranostic tool for precise cancer treatment.

Main Methods:

• Development of a small molecule Cbl-DEVD-Hcy designed for cascade response.
• In vivo testing in orthotopic breast tumor models.
• Utilizing near-infrared fluorescence and photoacoustic imaging to monitor apoptosis.

Main Results:

• Cbl-DEVD-Hcy releases chlorambucil (Cbl) upon cleavage by tumor carboxylesterase, inducing apoptosis.
• Activated caspase-3 triggers the production of Hcy-NH2, generating imaging signals.
• Demonstrated excellent theranostic correlation between imaging signals and therapeutic outcomes in vivo.

Conclusions:

• Cbl-DEVD-Hcy offers a promising approach for simultaneous cancer therapy and real-time in vivo treatment monitoring.
• The molecule facilitates precise evaluation of therapeutic effectiveness by correlating imaging signals with drug response.
• This theranostic strategy holds potential for advancing personalized cancer treatment and companion diagnostics.