Chemotherapeutic drug resistance poses a great challenge in
cancer therapy. Drug efflux and anti-apoptotic processes are the two most common mechanisms leading to
chemotherapy resistance. In this study, we focused on the applicability of
curcumin (CUR) as a sensitizer for chemotherapeutics (
doxorubicin [DOX] as the model drug) modified with
hyaluronic acid (HA) as an effective therapeutic strategy against multidrug resistance (MDR) in
cancer cells. We constructed an HA-CUR/DOX delivery system measuring approximately 180 nm with superior encapsulation efficacy and serum stabilities. In vitro, we found that HA modification could facilitate the efficient delivery of chemotherapeutics through CD44 receptor-mediated targeted delivery. MTT assay results confirmed that the combination of CUR and DOX/
paclitaxel (PTX) had a significant synergistic effect and significantly reversed MDR. Further experiments including real-time polymerase chain reaction and western blotting proved that the main mechanisms by which CUR reversed MDR in
tumor cells were inhibiting the expression and activity of
P-glycoprotein (P-gp) and inducing apoptosis through mitochondrial pathway. Taken together, our new engineered
tumor-targeting nanoparticle delivery system may have the potential for overcoming MDR in
cancer.