Natural fucoidan-based Cur nanoparticleas a biocompatibleand sustainable nanodrug for cancer-targeted therapy. Owing to great anticancer activity and excellent biosafety,curcumin(Cur) has potential development in cancer therapy. Nevertheless, theanticancer activity of Cur is limited by the poor selectivity towardtumors and low bioavailability. Inspired by coordination-driven self-assembly,it is a promising strategy for controlling drug delivery due to itsrich structure and properties, easy composition integration, and biodegradation.Here, a fucoidan-based Cur nanoparticle constructed from natural componentssynthesized via a green one-pot reaction of Cur, fucoidan (FU), andZn(2+) based on coordination-driven self-assembly, namely,FU/Zn2+/Cur-nanoparticles (FZC-NPs), was reported for improvingcancer therapy. The obtained FZC-NPs displayed a small hydrodynamicdiameter, high stability, high drug loading efficiency, glutathione(GSH)-triggered drug accurate release behaviors, fast intracellularuptake, and good penetrability ability into the tumor spheres. Comparedto free Cur, FZC-NPs had a stronger ability to induce mitochondrialdamage and inhibit tumor cell invasion and migration. The in vivoexperiments showed that FZC-NPs had effective accumulation in tumorsites, excellent antitumor activity, and good biocompatibility. Theseresults confirmed that the developed FZC-NPs is a safe and anticancerperformance therapeutic agent for cancer-targeted therapy.