Carrier-free zinc-baicalein nanoherbs inhibit osteosarcoma by modulating autophagy and Wnt/β-catenin pathway

The advancement of carrier-free nanosystems offers favorable tools for achieving cancer synergistic therapy, which is attributed to their simplified preparation and simple components. Recently, traditional Chinese herbal medicines (TCMs)-derived active molecules have become a research hotspot in carrier-free nanomaterials construction and anti-cancer application. Herein, the carrier-free zinc ion (Zn 2+ ), baicalein (BCL) self-assembly nanoframeworks (BCL-Zn) were prepared and Tanshinone IIA (TAN) was encapsulated in BCL-Zn to obtain TAN@BCL-Zn nanoherb for cancer synergetic therapy. After entering the slightly acidic tumor microenvironment, TAN@BCL-Zn nanoherbs degrade and cause the immediate release of the natural plant-derived active ingredients BCL and TAN. The natural plant-derived BCL not only serves as a component of the nanosystem, but also acts as a tumor-promoting Wnt/β-catenin pathway inhibitor. Meanwhile, Tanshinone IIA (TAN) acts as a dual-function agent, inducing excessive autophagy in osteosarcoma cells and thereby contributing to the enhanced antitumor performance of the nanoherbs. TAN@BCL-Zn nanoherbs presented excellent in vitro and in vivo anti-tumor efficacy. Our study demonstrates a metal-herb-based self-assembled strategy for osteosarcoma treatment through dual regulation of Wnt/β-catenin pathway and autophagy. This facile approach holds promise for promoting the development of nanotechnology-based cancer treatment. Construction of nanoherbs for osteosarcoma inhibition via regulating autophagy and Wnt/β-catenin pathway.