Ferrocene-conjugated polymeric platform via amide bond formation facilitates enhanced in situ fenton reaction and robust immune responses in combination with toll-like receptor 7/8 agonist

Abstract

Chemodynamic therapy (CDT) holds promise for catalyzing in situ Fenton/Fenton-like reactions by decomposing H2O2 to produce highly toxic hydroxyl radicals (•OH). As a CDT candidate, ferrocene (FcA)-based agents arouse extensive attention due to the stable divalent state of Fe2+. However, due to the pharmacokinetic and pharmacodynamic (PK/PD) characteristics of small molecules, how to increase the accumulation of FcA at tumor sites while maintaining high catalytic efficiency is still challenging. Herein, we designed a polymeric platform (N@Fc) to increase the tumor accumulation of FcA and induce improved catalytic efficiency. The FcA was conjugated to the biocompatible polymer via an amide bond, which served as an electron donor for the FcA group, thereby leading to higher electron density and catalytic efficiency. In combination with polymeric conjugated TLR7/8 agonist (IMDQ), N@Fc/IM could prime adaptive antitumor immunity by activating antigen-presenting cells and enhance the infiltration of T lymphocytes, and thus boosting robust immune response.