Photothermal amplification of Cu-porphyrin redox chemistry on Ti3C2 MXene for NIR-activated reactive oxygen species generation for the treatment of hepatocellular carcinoma.

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 and 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.