Conjugation of folic acid with TEMPO-oxidized cellulose hydrogel for doxorubicin administration

• Folic acid was grafted to TEMPO oxidized cellulose nanofibers forming a colloidal gel. • A novel delivery system can be formed by incorporating doxorubicin into the modified cellulose gel matrix. • The cellulose-folic acid system loaded with doxorubicin showed increased activity against eukaryotic normal and tumor cells when compared to free doxorubicin . The development of new drug delivery systems for cancer therapy is critical in order to further increase efficacy and reduce peripheral toxicity of current antitumor agents, and so far various targeting strategies have been investigated in this regard. Here we report on the synthesis and characterization of a new drug carrier system where folic acid is grafted at the surface of the oxidized cellulose nanofibers using the Diels Alder strategy. The oxidized cellulose nanofibers grafted with folic acid formed a colloidal system that was loaded with doxorubicin as a model antitumor agent. The system was tested in-vitro using both tumor and normal human cells, and results indicated an increased ability to kill human cells when compared to free doxorubicin. No significant effect of the CNF-bound folic acid causing an increased specificity towards tumor cells versus human fibroblast cells was observed, possibly as a result of a reduced binding potential of folic acid after conjugation to CNF. However, the system demonstrated an increased cellular uptake of doxorubicin by human cells, suggesting the potential to improve the therapeutic efficacy of pharmaceutical actives.