Details

Autor(en) / Beteiligte

• Teng, Clare W.
• Amirshaghaghi, Ahmad
• Cho, Steve S.
• Cai, Shuting S.
• De Ravin, Emma
• Singh, Yash
• Miller, Joann
• Sheikh, Saad
• Delikatny, Edward
• Cheng, Zhiliang
• Busch, Theresa M.
• Dorsey, Jay F.
• Singhal, Sunil
• Tsourkas, Andrew
• Lee, John Y. K.

Titel

Combined fluorescence-guided surgery and photodynamic therapy for glioblastoma multiforme using cyanine and chlorin nanocluster

Ist Teil von

• Journal of neuro-oncology, 2020-09, Vol.149 (2), p.243-252

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Introduction Glioblastoma multiforme (GBM) is the most common primary intracranial malignancy; survival can be improved by maximizing the extent-of-resection. Methods A near-infrared fluorophore (Indocyanine-Green, ICG) was combined with a photosensitizer (Chlorin-e6, Ce6) on the surface of superparamagnetic-iron-oxide-nanoparticles (SPIONs), all FDA-approved for clinical use, yielding a nanocluster (ICS) using a microemulsion. The physical–chemical properties of the ICS were systematically evaluated. Efficacy of photodynamic therapy (PDT) was evaluated in vitro with GL261 cells and in vivo in a subtotal resection trial using a syngeneic flank tumor model. NIR imaging properties of ICS were evaluated in both a flank and an intracranial GBM model. Results ICS demonstrated high ICG and Ce6 encapsulation efficiency, high payload capacity, and chemical stability in physiologic conditions . In vitro cell studies demonstrated significant PDT-induced cytotoxicity using ICS. Preclinical animal studies demonstrated that the nanoclusters can be detected through NIR imaging in both flank and intracranial GBM tumors (ex: 745 nm, em: 800 nm; mean signal-to-background 8.5 ± 0.6). In the flank residual tumor PDT trial, subjects treated with PDT demonstrated significantly enhanced local control of recurrent neoplasm starting on postoperative day 8 (23.1 mm 3 vs 150.5 mm 3 , p = 0.045), and the treatment effect amplified to final mean volumes of 220.4 mm 3 vs 806.1 mm 3 on day 23 (p = 0.0055). Conclusion A multimodal theragnostic agent comprised solely of FDA-approved components was developed to couple optical imaging and PDT. The findings demonstrated evidence for the potential theragnostic benefit of ICS in surgical oncology that is conducive to clinical integration.