Integrated theranostic nanoplatform empowers precision cancer care via radionuclide-labeled NIR-II aggregation-induced emission luminogens

Malignant tumours frequently evade conventional therapies due to their complexity and high recurrence rates. To overcome these limitations, an integrated theranostic nanoplatform was developed through modification of a NIR-II emitting aggregation-induced emission photosensitizer with folic acid and the polydentate ligand (DOTA), followed by radiolabeling with 68Ga. This strategy not only enhances cancer targeting precision but also confers superior positron emission tomography/computed tomography (PET/CT) imaging capabilities to the nanoparticles ([68Ga]DOTA-FA-BBTD-4C NPs). This nanoparticle demonstrates specific targeting and high-affinity binding to folate receptor alpha in glioblastoma cells, achieving clear tumour delineation by PET/CT imaging at 0.5 h post-injection and enabling accurate tumour resection guided by fluorescence imaging within a 12-h surgical window. Furthermore, the AIE-active photosensitizer-based platform simultaneously mediates synergistic phototherapy through localised hyperthermia and reactive oxygen species generation, effectively inducing apoptosis and cell cycle arrest to prevent tumour recurrence in female mice model. This multifunctional theranostic nanoplatform represents an advancement in cancer diagnosis and treatment, offering promising translational potential for clinical applications. Malignant tumours remain difficult to accurately diagnose, resect, and treat due to poor targeting, limited imaging depth, and high postoperative recurrence. The authors built a radionuclide labelled NIR-II AIE nanoplatform enabling PET/CT diagnosis, fluorescence guided surgery, and synergistic phototherapy that precisely treats tumours and prevents recurrence.