Palbociclib-derived multifunctional molecules for lysosomal targeting and diagnostic-therapeutic integration

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Lysosomal pH is crucial in tumor progression and drug resistance.
• Current methods for monitoring lysosomal pH in cancer therapy are insufficient.
• Targeted monitoring of lysosomal pH is needed for effective cancer treatment.

Purpose of the Study:

• To design and develop a novel molecule for real-time lysosomal pH monitoring.
• To integrate diagnostic and therapeutic functions for cancer therapy.
• To create a tool for tumor-targeted imaging and personalized treatment.

Main Methods:

• Covalent linkage of the anticancer drug palbociclib and fluorescein isothiocyanate (FITC).
• Design and development of a palbociclib-derived multifunctional molecule (Pal-FITC).
• Evaluation of Pal-FITC's fluorescence properties and pH response, and its effect on cell cycle.

Main Results:

• Pal-FITC exhibits a 20-fold increase in fluorescence compared to FITC.
• Pal-FITC demonstrates a linear fluorescence response across a pH range of 4.0-8.2 (R² = 0.9901).
• Pal-FITC effectively inhibits cell cycle progression by blocking cells in the G1 phase via the Cyclin D-CDK4/6-Rb pathway.

Conclusions:

• The developed Pal-FITC molecule offers enhanced fluorescence for lysosomal pH monitoring.
• Pal-FITC shows potential for dual diagnostic and therapeutic applications in cancer.
• This study presents a novel strategy for tumor-targeted imaging and personalized cancer therapy.