Combined fluorescence-guided surgery and photodynamic therapy for glioblastoma multiforme using cyanine and chlorin nanocluster
| Autor: | Clare W Teng, Andrew Tsourkas, Steve S. Cho, John Y K Lee, Shuting S. Cai, Theresa M. Busch, Edward J. Delikatny, Yash Singh, Saad Sheikh, Ahmad Amirshaghaghi, Joann Miller, Zhiliang Cheng, Jay F. Dorsey, Emma De Ravin, Sunil Singhal |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Porphyrins medicine.medical_treatment Apoptosis Photodynamic therapy Malignancy Fluorescence Neurosurgical Procedures Theranostic Nanomedicine Article Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Surgical oncology Tumor Cells Cultured Animals Humans Medicine Photosensitizer Coloring Agents Cell Proliferation business.industry Carbocyanines medicine.disease Combined Modality Therapy Xenograft Model Antitumor Assays Mice Inbred C57BL Photochemotherapy Surgery Computer-Assisted Neurology Oncology chemistry 030220 oncology & carcinogenesis Chlorin Nanoparticles Female Neurology (clinical) Glioblastoma business Nuclear medicine 030217 neurology & neurosurgery |
| Zdroj: | J Neurooncol |
| ISSN: | 1573-7373 0167-594X |
| Popis: | 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: 745nm, em: 800nm; 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 (23.1mm(3) vs 150.5mm(3), p=0.045), and the treatment effect amplified to final mean volumes of 220.4mm(3) vs 806.1mm(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. |
| Databáze: | OpenAIRE |
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