Spatiotemporal Regulation of Ferrocene-Based MOFs: Harnessing Photothermal “Local Storm” and “Systemic Immune Cruise

Abstract

Ovarian cancer ranks among the most prevalent gynecologic malignancies, characterized by a high incidence and poor prognosis. However, the efficacy of conventional chemotherapy is often compromised by systemic toxicity and insufficient immune activation. To address these challenges, a zirconium-ferrocenyl metal–organic framework modified with the immune adjuvant glucan (Zr-Fc-MOF@Glu) was rationally designed to enable spatiotemporally controlled photothermal immunotherapy. Upon near-infrared (NIR) irradiation, Zr-Fc-MOF@Glu generates a localized photothermal effect, inducing tumor cell apoptosis and triggering an inflammatory “storm” within the tumor microenvironment. Concurrently, the glucan component acts as an immunomodulator, amplifying immune activation and initiating a robust systemic immune response, thereby enabling a “systemic immune cruise.” Both in vitro and in vivo evaluations demonstrated that this approach effectively inhibited tumor growth, enhanced immune responses, and minimized adverse effects. By integrating photothermal-induced local inflammatory activation with systemic immune mobilization, this strategy presents a promising avenue for precise and efficacious ovarian cancer therapy.