Metallopolysaccharide-Based Smart Nanotheranostic for Imaging-Guided Precise Phototherapy and Sequential Enzyme-Activated Ferroptosis.

Phototheranostic offers a regional-focused tumor treatment upon photoirradiation. However, it is difficult to completely eradicate solid tumors using a conventional phototheranostic owing to the residual tumor cells outside the laser irradiation range. Herein, we fabricated a metallopolysaccharide-based smart nanotheranostic (Fe- d HA) via a nanoassembly-driven method, in which Fe 3+ ions were coordinated to dopamine-modified biopolysaccharide hyaluronic acid ( d HA). Taking advantage of the structural backbone and intrinsic dual-information-related functions of HA as well as the bi-functional Fe(III)-coordination centers, Fe- d HA can efficiently target tumor cells for phototheranostic. Additionally, it can be activated by endogenous overexpressed hyaluronidase to achieve sequential ferroptosis in tumor cells. The precise imaging and effective tumor inhibition using this metallopolysaccharide-based nanotheranostic were significantly demonstrated in vivo and in vitro. Thus, this rationally designed Fe- d HA provided a simple metallopolysaccharide strategy to develop an "all-in-one" smart nanotheranostic to synergize different therapeutic modalities for improving cancer therapy.