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

Abstract 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) NaGdF 4 :Nd/Yb/Tm with up/down dual‐mode conversion luminescence. The theranostic agent was further decorated with D‐type neuropeptide D NPY 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.