Docetaxel combined with silver nanoparticles for synergistic therapy of prostate cancer via effectively inhibiting cell proliferation and inducing apoptosis

Hyaluronan-chitosan-silver-Prussian blue@docetaxel nanoparticles (HA-Ag-PB@DTX NPs) demonstrated a synergistic effect in tumor eradication, with controlled drug release and targeted tumor cell penetration and localization abilities. Moreover, these NPs exhibited significant tumor growth inhibition in PC-3 heterotopic animal models by inducing apoptosis. Safety evaluations both in vitro and in vivo confirmed that HA-Ag-PB@DTX NPs significantly mitigated the toxic and side effects associated with DTX. Overall, this synergistic chemotherapy approach shows remarkable anti-tumor efficacy, offering a promising alternative to PCa therapy. • HA-Ag-PB@DTX NPs demonstrated a synergistic effect in tumor eradication with favorable targeting abilities. • HA-Ag-PB@DTX NPs with high biosafety significantly mitigated the toxic of DTX by controllable drug release. • HA-Ag-PB@DTX NPs exhibited tumor growth inhibition in PC-3 heterotopic animal models by inducing apoptosis and tumor penetration. Although docetaxel (DTX) is a first-line chemotherapeutic agent for treating prostate cancer (PCa), its clinical effectiveness is hampered by patients developing resistance following long-term, high-dose use. Additionally, its low bioavailability and significant toxicity further restrict its therapeutic potential. To address these issues, we developed hyaluronan (HA)-modified Prussian blue nanoparticles (PB NPs) that co-load DTX and chitosan-encased silver nanoparticles (Chi-Ag NPs), aimed at enhancing solubility, targeting capability, and therapeutic efficacy. In vitro assays demonstrated that HA-Ag-PB@DTX NPs could synergistically kill PC-3 cells by effectively targeting tumor cells and inducing cell apoptosis. In vivo studies showed that HA-Ag-PB@DTX NPs significantly inhibited tumor growth in heterotopic tumor-bearing mice through enhanced penetrability in tumor tissues and synergistic effects. Furthermore, these NPs markedly reduced the toxicity of DTX due to their controlled release and targeted delivery mechanisms. In conclusion, we have successfully developed novel nanocomplexes that improve the dosage of DTX and provide a synergistic approach for PCa therapy.