D-type neuropeptide decorated AIEgen/RENP hybrid nanoprobes with light-driven ROS generation ability for NIR-II fluorescence imaging-guided through-skull photodynamic therapy of gliomas

Glioma is one of the most common malignant tumors of the central nervous system, leading high mortality rates in human. Aggregation-induced emission (AIE) photosensitizers-based photodynamic therapy (PDT) has emerged as a promising therapeutic strategy for least-invasive treatment of glioma, which involves local irradiation of the tumor using an external near-infrared (NIR) laser. Unfortunately, most AIE photosensitizers suffered from poorly penetration of the visible light excitation, bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier (BBB) crossing ability, which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor treatment. In this work, we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles (RENPs) NaGdF₄:Nd/Yb/Tm with up/down dual-mode conversion luminescence. The theranostic agent was further decorated with D-type neuropeptide ^DNPY for crossing BBB and targeting glioma. Under the 808-nm light irradiation, the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ. These results demonstrate that the integration of D-type neuropeptide, AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.