Photothermal Amplification of Cu-Porphyrin Redox Chemistry on Ti₃C₂ MXene for NIR-Activated Reactive Oxygen Species Generation for the Treatment of Hepatocellular Carcinoma

Abstract

Controlled generation and regulation of reactive oxygen species (ROS) remains challenging when photochemical and redox processes are combined for cancer-related applications. Photothermal regulation of metal-centred redox kinetics provides a route to amplified ROS (¹O₂, •OH, O₂•⁻ , etc.) generation in hybrid inorganic systems. In such systems, transition metal-mediated ROS generation is intrinsically governed by local coordination environments, redox kinetics, and energy-transfer pathways. Herein, we report a stepwise-assembled Ti₃C₂@UCNP@Cu-TCPP@LA system in which the redox chemistry of Cu(II)-tetrakis(4-carboxyphenyl)porphyrin (Cu-TCPP) is kinetically regulated by plasmon-assisted photothermal activation of Ti₃C₂ MXene under near-infrared (808 nm) irradiation. Ti₃C₂ nanosheets were integrated with aminated NaYF₄:Yb³⁺/Er³⁺/Nd³⁺ upconversion nanoparticles (UCNPs) through interfacial hydrogen bonding. UCNPs serve as NIR-to-visible photonic intermediates for activating spatially segregated Cu-TCPP moieties covalently attached to the UCNP surface. This architecture suppresses π-π aggregation-induced ROS quenching, preserves the excited-state dynamics of Cu-TCPP, and facilitates efficient Förster resonance energy transfer (FRET) from the UCNPs. Under 808 nm irradiation, the integrated Ti₃C₂ component exhibits pronounced plasmon-derived photothermal behaviour (photothermal conversion efficiency ≈57%), which kinetically accelerates singlet oxygen (¹O₂) generation from photoexcited Cu-TCPP. Simultaneously, photothermal heating promotes intracellular Cu²⁺/Cu⁺ redox cycling, accelerates glutathione depletion and Fenton-like hydroxyl radical (•OH) production, collectively amplifying chemodynamic reactivity. Ti₃C₂-mediated photothermal activation yields ~4-fold higher ¹O₂ and ~3-fold greater •OH generation than the UCNP@Cu-TCPP@LA system. Beyond photothermal activation, Ti₃C₂ serves as a conductive support that facilitates interfacial charge and energy transfer processes under NIR irradiation. Functionalisation with lactobionic acid (LA) improves aqueous dispersibility and enables receptor-mediated cellular uptake. In vitro studies confirm pH-responsive behaviour, efficient intracellular ROS generation, and significant cancer cell apoptosis (~78%) under 808 nm excitation, highlighting the functional relevance of plasmon-assisted photothermal amplification of Cu-porphyrin redox chemistry on Ti₃C₂.