Hypocrellin-Based Multifunctional Phototheranostic Agent for NIR-Triggered Targeted Chemo/Photodynamic/Photothermal Synergistic Therapy against Glioblastoma

A huge challenge exists in the diagnosis and treatment of malignant glioblastoma (GBM) due to the presence of the blood-brain barrier (BBB). Herein, a multifunctional phototheranostic agent is designed on the basis of an octadecane-modified temozolomide ( ) for chemotherapy, a dicysteamine-modified hypocrellin derivative ( ) as a natural-origin photosensitizer with a singlet oxygen ( O ) quantum yield of 0.51, and a cyclic peptide (cRGD) as a targeting unit against glioblastoma. Co-encapsulated and assembly with cRGD decoration, referred to as , shows a wide absorption at the NIR region peaked at 703 nm, an NIR emission peak at 720 nm, good photostability, high photothermal conversion efficiency (33%), and effective degradation of . More importantly, can efficiently break through the blood-brain barrier and enrich in the orthotopic glioblastoma. The treatment of subcutaneous U87MG tumor beard mice demonstrates that present remarkable anticancer efficiency and the targeted chemo/photodynamic/photothermal synergistic therapy can be achieved with almost no toxicity. This multifunctional phototheranostic agent shows great potential for the diagnosis and treatment of glioblastoma.