Hyaluronic acid coated nano-particles for H₂O₂-elevation augmented photo-/chemodynamic therapy

In recent years, the association of chemodynamic therapy (CDT) with photodynamic therapy (PDT) has attracted much attention due to their mutually reinforced property. Nevertheless, how to further strengthen their performance is still a big challenge. Given the PDT/CDT therapeutic mechanism, the H₂O₂ amount might affect their final performance. Thus, in this paper, our synthesized pH-responsive Fenton agents (ferrocene-cinnamaldehyde conjugates, Fc-CA) were encapsulated in hyaluronic acid (HA) coated porphyrin-based MOF to obtain supramolecular nano-particles (Fc-CA-PCN-HA). After the CD44-receptor mediated internalization, the released Fc-CA could further dissociate in the acidic pH micro-environment. The released CA can activate the NADPH oxidase to elevate the H₂O₂ amount which could be preferable to produce more ·OH through Fenton reaction for cancer cells apoptosis. Additionally, O₂ was also generated in the CDT which could alleviate tumor hypoxia condition and be provided as the reactant for PDT to produce more ¹O₂. Thus, given the excellent cascade reactions induced therapeutic performance of Fc-CA-PCN-HA in vitro and in vivo, the H₂O₂-elevation strategy might further enhance the PDT/CDT outcomes.