Biodegradable neodymium metal-organic frameworks for persistent NIR-II fluorescence imaging-guided photodynamic therapy with glutathione exhaustion

Rare-earth-based near-infrared (NIR) fluorescence probes with narrow multi-peak emission, long luminescence lifetimes, and high photostability are highly desirable for bioimaging. Nevertheless, such probes remain largely underdeveloped due to poor biodegradability, sophisticated synthetic procedures, and complicated photophysical modulation. Herein, neodymium (Nd) was screened from the entire series of lanthanide-containing rare-earth elements, and we developed Nd-tetrakis(4-carboxyphenyl) porphyrin (TCPP) metal-organic framework (MOF) nanoprobes. Interestingly, within this MOF assembly, the Nd-TCPP coordination creates a highly ordered rigid architecture, suppressing non-radiative transitions and dramatically boosting NIR-II emission peaking at 1060 nm. Benefiting from spatial confinement and close donor-acceptor proximity, the proposed resonant 4f-to-triplet energy transfer (f-TET) from excited Nd 3+ to TCPP is suggested to be efficiently triggered under 808 nm laser irradiation, activating photodynamic processes to generate singlet oxygen ( 1 O 2 ). The synthesized NTM was subsequently loaded with L-buthionine sulfoximine (BSO) followed by PEGylation to obtain NTMBP nanoprobes. Upon systemic administration, the nanoprobes efficiently accumulated at tumor sites and produced durable, bright NIR-II fluorescence under 808 nm laser excitation, enabling clear visualization of tumor boundaries for precise phototherapy guidance. Meanwhile, under irradiation with the same wavelength, the NTMBP nanoprobes could generate 1 O 2 for tumor photodynamic therapy (PDT). In addition, BSO could deplete intracellular glutathione (GSH) to weaken antioxidant defenses, amplifying oxidative stress, and inducing robust tumor cell death. Our nanoprobe with favorable biocompatibility and biodegradability exhibited outstanding capabilities for NIR-II fluorescence imaging-guided PDT, holding great promise for further precise cancer theranostics.