Orthogonal upconversion mimicking Nd-Mn heterometallic nanocomposite for dual NIR responsive self-amplifying...

Shallow tissue penetration of excitation light remains the most persistent barrier to effective photodynamic therapy (PDT), compounded further by tumour hypoxia and elevated glutathione (GSH). Herein, we report a rationally engineered core-shell nanoplatform comprising a Mn-centred porphyrinic metal-organic framework constructed from Nd³⁺ coordination nodes (MN-MOF) and integrated with NaYbF₄:Tm upconversion nanoparticles (UCNPs). The strategic integration of neodymium (Nd) as the Nd-porphyrin MOF contributes towards bandgap modulation and photophysical optimization necessary to achieve FRET derived orthogonality. Consequent activation of discrete luminescent channels within a single nanoparticle using different wavelengths (980 nm/808 nm) of light facilitates cytotoxic singlet oxygen (¹O₂) generation. The incorporation of Mn into the porphyrinic centre facilitates efficient Mn³⁺/Mn²⁺ redox cycling, driving Fenton-like reactions that generate hydroxyl radicals (˙OH) while depleting intracellular GSH, thereby enhancing oxidative stress. Concurrently, Mn catalyses the decomposition of endogenous H₂O₂ to generate O₂, relieving tumour hypoxia and promoting ¹O₂ generation. Furthermore, lactobionic acid (LA) functionalised UCNP@MN (UMNL) demonstrates ASGPR receptor-mediated selective elimination of hepatic cancer cells (cell death ∼64-70%). Overall, this work provides a novel coordination-driven approach towards near infrared (NIR) light-activated multifunctional nanoplatforms that overcome tumour microenvironment (TME) associated challenges while enhancing the synergistic efficacy of chemodynamic and photodynamic therapy.