Smart Solid Drug Delivery Systems: Exploring the pH Sensitivity of Cashew Gum‑Doxorubicin Prodrug

Polysaccharide-based prodrugs formed via pH-responsive covalent interactions can be used to prepare nanoparticles for drug delivery to tumor cells. This study reports the synthesis of cashew gum-doxorubicin prodrugs via Schiff base (CG-S-DOX) and amide bonds (CG-A-DOX), both of which exhibit pH-responsive behavior. Synthesis was confirmed using spectroscopic techniques. Drug-binding content and efficiency were higher for CG-S-DOX than for CG-A-DOX. The capacity of the nanoparticles to self-organize in aqueous media was confirmed using fluorescence spectroscopy, dynamic light scattering, and atomic force microscopy. Both prodrugs possessed sizes < 200 nm and showed responsive doxorubicin-release profiles in the acidic tumor cell microenvironment. Compared with free DOX, the CG-S-DOX and CG-A-DOX prodrug had significantly reduced cytotoxicity against non-tumor cells (L929). CG-S-DOX, but not CG-A-DOX, showed antitumor activity against HCT-116 (human colorectal cancer) and MCF-7 (human breast cancer) cells. An uptake assay confirmed that the nanoparticles were easily taken up by HCT-116 cells. These results together with the great reduction in cytotoxicity against non-tumor cells, confirm the potential of CG-S-DOX prodrug nanoparticles as a reliable and efficient system for the effective delivery of doxorubicin to tumor cells.