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- Title
Combined fluorescence-guided surgery and photodynamic therapy for glioblastoma multiforme using cyanine and chlorin nanocluster.
- Authors
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.
- Abstract
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 mm3 vs 150.5 mm3, p = 0.045), and the treatment effect amplified to final mean volumes of 220.4 mm3 vs 806.1 mm3 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.
- Subjects
GLIOBLASTOMA multiforme; PHOTODYNAMIC therapy; UNITED States. Food &; Drug Administration; INTRACRANIAL tumors; TREATMENT effectiveness; CYANINES
- Publication
Journal of Neuro-Oncology, 2020, Vol 149, Issue 2, p243
- ISSN
0167-594X
- Publication type
Article
- DOI
10.1007/s11060-020-03618-1