Cellulose nanocrystals-based fluorescent biocarrier binding GAPDH protein with high affinity in cancer-target doxorubicin delivery

Cellulose nanocrystals (CNCs) have shown immense promise in medical applications, especially in cancer treatment, owing to their excellent biocompatibility and potential for functional modifications. Considering the crucial role of the protein reduced glyceraldehyde-phosphate dehydrogenase (GAPDH) in cancer progression, we embarked to immobilize CNCs with GAPDH and fluorescent molecules FITC, creating FCNC-G through regioselective modifications. Furthermore, an accelerated proliferation of cancer cells was observed in the presence of FCNC-G. To evaluate the therapeutic potential of FCNC-G, we loaded it with doxorubicin (DOX) to create FCNC-G-D and tested its effect on Hepg2. We observed a significant inhibition of Hepg2 cells exposed to low concentrations of FCNC-G-D. Additionally, mitochondrial dysfunction was detected in Hepg2 and Cal27 cells, treated with FCNC-G-D, but not in A375 cells, further highlighting its selective impact on cancer cells. Given the limitations of DOX in clinical applications, our findings establish a strong foundation for further research on the potential of CNCs grafted with GAPDH as a novel cancer-targeted biocarrier with high affinity. The combination of CNCs unique properties with targeted delivery strategies holds tremendous promise for the development of more effective and safer cancer therapies.