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

Chuangli ZhangJiasheng WuWeimin LiuXiuli ZhengWenjun ZhangChun-Sing LeePengfei Wang
Published in: ACS applied bio materials (2020)
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 ( 1 O 2 ) 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.
Keyphrases
  • cancer therapy
  • photodynamic therapy
  • drug delivery
  • drug release
  • fluorescence imaging
  • oxidative stress
  • molecular dynamics
  • stem cells
  • metabolic syndrome
  • insulin resistance