Doxorubicin/cisplatin co-loaded hyaluronic acid/chitosan-based nanoparticles for in vitro synergistic combination chemotherapy of breast cancer

•DOX/CDDP-loaded polysaccharide-based nanovehicles were successfully prepared.•CDDP crosslinking enhanced the stability of NPHER2(DOX/CDDP).•CDDP and DOX were loaded onto AHA by chelation and Schiff’s base, respectively.•Nanoparticles composed of drug core and polysaccharide shell were fabricated.•Co-delivery of DOX and CDDP achieved great synergistic anticancer effect. Combination chemotherapy has attracted more and more attention in the field of anticancer treatment. Herein, a synergetic targeted combination chemotherapy of doxorubicin (DOX) and cisplatin in breast cancer was realized by HER2 antibody-decorated nanoparticles assembled from aldehyde hyaluronic acid (AHA) and hydroxyethyl chitosan (HECS). Cisplatin and DOX were successively conjugated onto AHA through chelation and Schiff’s base reaction, respectively, forming DOX/cisplatin-loaded AHA inner core. The core was sequentially complexed with HECS and targeting HER2 antibody-conjugated AHA. The formed near-spherical nanoplatform had an average size of ∼160 nm and a zeta potential of −28 mV and displayed pH-responsive surface charge reversal and drug release behaviors. HER2 receptor-mediated active targeting significantly enhanced the cellular uptake of nanoplatform. Importantly, DOX and cisplatin exhibited a synergistic cell-killing effect in human breast cancer MCF-7 cells. These results clearly indicate that the novel nanoplatform is promising for synergistic combination chemotherapy of breast cancer.