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

Posted on 2020-05-31 - 12:03
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 (TMZ-C18) for chemotherapy, a dicysteamine-modified hypocrellin derivative (DCHB) as a natural-origin photosensitizer with a singlet oxygen (1O2) quantum yield of 0.51, and a cyclic peptide (cRGD) as a targeting unit against glioblastoma. Co-encapsulated DCHB and TMZ-C18 assembly with cRGD decoration, referred to as DTRGD NPs, 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 TMZ-C18. More importantly, DTRGD NPs can efficiently break through the blood–brain barrier and enrich in the orthotopic glioblastoma. The treatment of subcutaneous U87MG tumor beard mice demonstrates that DTRGD NPs 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.

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