Manipulation of Energy Migration in Upconversion Nanoparticles for Long-Lived Mn²⁺ Emission and Enhanced Singlet Molecular Oxygen Generation

Nanosensitizers having long-lived upconversion emission under near-infrared (NIR) excitation offer unique advantages in terms of reduced background noise and prolonged signal detection for deep tissue therapy of cancer. Herein, we demonstrate a systematic mechanism of energy migration toward achieving long-lived Mn2+ upconversion emission in the multilayered core–shell–shell lattice of NaGdF4:Yb3+,Tm3+,Ca2+/NaGdF4:Yb3+,Ca2+/NaGdF4:Mn2+ upconversion nanoparticles (NPs), following the Yb3+ → Tm3+ → Gd3+ → Mn2+ intermetal ions energy transfer pathway. Furthermore, a rational design of nanosensitizer was achieved by incorporating Er3+ ions into the intermediate shell of multishell NPs, which was subsequently conjugated with the Rose Bengal sensitizer to enable the enhancement in singlet molecular oxygen (1O2) generation under excitation of a 980 nm NIR laser. An intense higher-energy emission in the UV–blue visible region from Tm3+ was achieved by optimizing the amount of Ca2+ in the core–shell NPs, followed by subsequent energy migration to the Mn2+ ion incorporated at the outer shell. The Mn2+ ions were strategically doped in the outer shell of NPs to leverage the catalytic activities of Mn2+ for H2O2 decomposition and decrease the backward energy transfer to the Tm3+ ion. Hence, this approach resulted in a long lifetime of Mn2+ (∼34 ms), attributed to the spin-forbidden 4T1g → 6A1g transition within 3d5 configuration. Additionally, the nanosensitizer demonstrated high 1O2 (∼0.39 μM) generation even at a very low concentration (5 μg/mL) under a laser power of 2 mW cm–2. The hydrogenase-like catalytic activities of Mn2+ exhibited significant oxygen production through decomposition of H2O2. Hence, these findings might contribute to the development of convenient multifunctional nanosensitizers for multimodal bioimaging and therapeutic features, including efficient 1O2 generation and catalytic decomposition of H2O2 (found excessively in a tumor environment) to oxygen for alleviating the hypoxia.