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

<b>Aim:</b> Lysosomal pH changes are associated with drug resistance, cell growth and invasion of tumors, but effective and specific real-time monitoring of lysosomal pH compounds for cancer therapy is lacking. <b>Materials &amp; methods:</b> Here, based on the covalent linkage of the anticancer drug palbociclib and fluorescent dye fluorescein isothiocyanate (FITC), we designed and developed a novel palbociclib-derived multifunctional molecule (Pal-FITC) for lysosomal targeting and diagnostic therapeutic integration. <b>Results &amp; discussion:</b> Pal-FITC fluoresces is 20-fold stronger than that of FITC and shows a linear response in the pH range of 4.0–8.2 (R² = 0.9901). Pal-FITC blocks cells in G1 phase via <i>Cyclin D-CDK4/6-Rb</i>. <b>Conclusion:</b> Our study provides new strategies for tumor-targeted imaging and personalized therapy. Based on the covalent linkage of the anticancer drug and the fluorescent dye, we designed and developed a novel palbociclib-derived multifunctional molecule (Pal-FITC) for lysosomal targeting and diagnostic therapeutic integration. Pal-FITC responded linearly in the pH range of 4.0–8.2. In addition, Pal-FITC was able to effectively treat lung cancer without toxic side effects on normal cells. It has a significant cell cycle blocking phenomenon and blocks G1 phase cells via <i>Cyclin D-CDK4/6-Rb</i>. Our study provides a new strategy for tumor-targeted imaging and personalized therapy. Based on the covalent linkage of the anticancer drug palbociclib and the fluorescent dye fluorescein isothiocyanate (FITC), we design and develop a novel palbociclib-derived multifunctional molecule for lysosomal targeting and diagnostic therapeutic integration (Pal-FITC), which can be used for lysosome-targeted imaging, pH monitoring and treatment of non-small-cell lung cancer (NSCLC). Pal-FITC can effectively target lysosomes. The fluorescence intensity of Pal-FITC is more than 20-fold stronger than that of FITC and shows a linear response in the pH range of 4.0–8.2 (R² = 0.9901), which can be used as a pH sensor to monitor lysosomal pH changes in real time. Pal-FITC was found to have anticancer effects similar to those of palbociclib. Pal-FITC has low toxicity. Pal-FITC had a significant cell cycle-blocking phenomenon and blocked cells in the G1 phase via <i>Cyclin D-CDK4/6-Rb</i>. Our study provides new strategies for tumor-targeted imaging and personalized therapy.