The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement. Zinc ions have been reported to stimulate angiogenesis, but application was limited to the toxicity concerns. We hypothesized that zinc based metal-EGCG capsule (EGCG/Zn Ps) can achieve sustained release Zn2+ resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG. The surface morphology, zeta potential, infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured. In vitro, EGCG/Zn showed significantly antioxidant, anti-inflammatory and induced cell migration effect. In addition, EGCG/Zn Ps enabled the sustained release of zinc ions, which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor (VEGF) in vitro and in vivo. In mouse models of limb ischemia, EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues. Moreover, EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score, limb temperature and blood flow than other groups. In conclusion, EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn2+ and EGCG, thus enabling the direct application to limb ischemia.

Reactive oxygen species (ROS)-responsive nanocapsules for cancer drug delivery were engineered from green tea polyphenol–metal networks. Briefly, DOX-doped ZIF-8 nanoparticles were synthesized via coprecipitation and coated with a layer of EGCG–Fe(III) complexes by suspending in EGCG and ferric chloride aqueous solutions under mild conditions. The DOX-encapsulating EGCG/Fe nanocapsules (DOX@EGCG/Fe NCs) with a diameter of 399 nm were obtained after template removal. The as-prepared EGCG/Fe NCs can reduce ROS potential accompanied by their degradation. Moreover, DOX@EGCG/Fe NCs can be quickly internalized by cancer cells, and then the intracellular drug release was greatly accelerated in response to overproduced ROS of tumor. Owing to higher ROS levels inside tumor cells compared with normal cells, DOX@EGCG/Fe NCs cause selective cytotoxicity for tumor cells over normal cells. Furthermore, the cytotoxicity of DOX@EGCG/Fe NCs was increased with the increasing incubation time with cancer cells, whereas the tendency of free DOX was reversed. Accordingly, DOX@EGCG/Fe NCs demonstrate good tumor growth inhibition (84.2%) with minor systemic toxicity, which would be a promising candidate for B16 melanoma therapy. Hopefully, our approach could be extended to many other delivery systems such as water soluble/insoluble drugs, gene and protein due to the diversity of polyphenol–metal networks and ZIF-8 templates.