Targeted Europium Chelation: A Strategy for Intervening Tumor Extracellular Matrix.

Abstract

As an important component of the tumor microenvironment, the extracellular matrix (ECM) generally undergoes extensive remodeling, acting as a shield to block drug delivery and immune recognition. Currently, ECM-clearing strategies for tumor treatment still face challenges. In this work, a type of europium metal-organic nanowire was prepared for targeting the highly expressed sialic acid (SA) on glycoproteins within the ECM. The nanowire, termed TFE, was prepared by coordination reaction of thiodiacetic acid (TDA) with Fe³⁺ and Eu³⁺. Eu³⁺ can competitively chelate to the highly expressed SA in ECM, leading to the release of Eu³⁺ from TFE. The precursors of the TFE can be injected directly into the tumor site, forming a gel-like morphology within ∼1 min. The TFE can effectively encapsulate cancer cells, disrupt the ECM integrity, and stimulate immune recognition and ferroptosis. Moreover, the TFE demonstrated dual diagnostic and therapeutic capabilities by embedding fluorescent drugs, such as doxorubicin (DOX), enabling ECM-targeted theranostics.