pH-responsive glycodendrimer as a new active targeting agent for doxorubicin delivery.

The present study synthesized a new kind of pH-responsive active targeting glycodendrimer (ATGD) for doxorubicin delivery to cancerous cells. First, the glycodendrimer was synthesized based on the cultivation of chitosan dendrons on amine-functionalized, silica-grafted cellulose nanocrystals. Afterward, glycodendrimer was conjugated with folic acid to provide a folate receptor-targeting agent. The response surface method was employed to obtain the optimum conditions for the preparation of doxorubicin-loaded ATGD. The effect of doxorubicin/ATGD ratio, temperature, and pH on doxorubicin loading capacity was evaluated, and high loading capacity was achieved under optimized conditions. After determining doxorubicin release pattern at acidic and physiological pH, ATGD cytotoxicity was surveyed by MTT assay. Based on the results, the loading behavior of doxorubicin onto ATGD was in good agreement with monolayer-physisorption, and drug release was Fickian diffusion-controlled. ATGD could release the doxorubicin much more at acidic pH than physiological pH, corresponding to pH-responsive release behavior. Results of MTT assay confirmed the cytotoxicity of doxorubicin-loaded ATGD in cancer cells, while ATGD (without drug) was biocompatible with no tangible toxicity. These results suggested that ATGD has the potential for the treatment of cancer. [Display omitted] • Glycodendrimer was successfully synthesized via the cultivation of chitosan dendrons on CNC. • Folic acid as targeting ligand was conjugated to glycodendrimer to form ATGD. • ATGD could load doxorubicin with high capacity. • ATGD has pH-responsive property for doxorubicin release. • In vitro cellular studies, proved that doxoribucin loaded ATGD could be considered as therapeutic agent. [ABSTRACT FROM AUTHOR]