Sydney Zhou

Introduction. Glioblastoma multiforme (GBM) has a median survival of 9-12 months and is a challenging cancer to diagnose and treat.¹ Prognosis is significantly improved with >98% extent of resection (EOR).² However, limitations of imaging modalities such as magnetic resonance (MR) imaging and computed tomography (CT) hinder the differentiation of malignant and normal tissue pre- and intra-operatively.³ Nanotechnology, the design of materials within the 1-100 nm size range, has been studied to improve diagnosis and treatment of GBMs by enabling multimodal imaging, improving intraoperative visualization, and acting as phototherapeutic agents.^4,5,6,7 Further knowledge about the diagnostic and therapeutic properties of nanoparticles could lead to improved GBM prognosis.

Methods. Research papers published within the past 5 years were identified in PubMed and Google Scholar using keywords searches for different combinations of the terms: glioblastoma, glioma, nanotheranostic, nanoparticle, imaging, and multimodal imaging. The search yielded papers on 1) TB1 dots – high fluorescence quantum yield aggregation-induced-emission dots⁴ 2) Au@MIL-99(Fe) – core-shell gold nanorod metal-organic framework nanoprobes⁵ 3) manganese (Mn) doped carbon dots (CDs)⁶ and 4) ICG/AuNR@BCNP – biomimetic catalase-integrated-albumin photheranostic nanoprobes.⁷ In all studies, nanoparticles were first synthesized, subjected to optical property characterization, and assayed for cytotoxicity.^4,5,6,7 In-vitro studies assessed imaging capabilities, cellular uptake, and phototherapeutic efficacy^4,5,7 before nanoparticles were injected into U86 or U87 tumor bearing mice for in-vivo assessment of imaging capabilities and phototherapy efficacy.^4,5,6,7 In ex-vivo studies, mice brains treated with Mn doped CDs and ICG/AuNR@BCNP were excised to evaluate image-guided resection capabilities.^6,7

Results. TB1 dots enabled dual-modal NIR-I and NIR-II fluorescence imaging by achieving a high quantum yield and a large absorptivity at 740 nm, allowing tumor detection through an intact scalp and skull in mice models.⁴ For triple-modality imaging, Au@MIL-99(Fe) had high spatial resolution, contrast, and depth of penetration on CT, MR, and photoacoustic (PA) imaging.⁵ Mn-doped carbon dots exhibited high MRI relaxivity and a distinct excitation dependent photoluminescence in ex-vivo optical imaging.⁶ ICG/AuNR@BCNP achieved high penetration depth and signal-to-background ratio in fluorescence, PA, and thermal imaging while simultaneously generating reactive oxygen species for pre- and post-operative phototherapy, thereby inhibiting glioma growth, extending survival, and improving apoptosis.⁷

Conclusion. Nanotechnology is a key area of development for pre-, intra-, and post-operative GBM management. Multi-modal pre-operative imaging allows surgeons to better plan for tumor resection,⁸ while improved intra-operative visualization can increase EOR.² Finally, nanotheranostics are promising agents for earlier detection and simultaneous treatment of GBMs, which may significantly improve prognosis.⁷

Work Cited:

1. Rajesh, Y., Pal, I., Banik, P. et al. Insights into molecular therapy of glioma: current challenges and next generation blueprint. Acta Pharmacol Sin 38, 591–613 (2017). https://doi.org/10.1038/aps.2016.167
2. Schipmann S, Schwake M, Suero Molina E, Stummer W. Markers for identifying and targeting glioblastoma cells during surgery. Journal of Neurological Surgery Part A: Central European Neurosurgery. 2019;80(06):475-487. doi:10.1055/s-0039-1692976
3. Wu X, Yang H, Yang W, et al. Nanoparticle-based diagnostic and therapeutic systems for brain tumors. J Mater Chem B. 2019;7(31):4734-4750. doi:10.1039/c9tb00860h
4. Sheng Z, Guo B, Hu D, et al. Bright Aggregation-Induced-Emission Dots for Targeted Synergetic NIR-II Fluorescence and NIR-I Photoacoustic Imaging of Orthotopic Brain Tumors [published online ahead of print, 2018 May 28]. Adv Mater. 2018;e1800766. doi:10.1002/adma.201800766
5. Shang W, Zeng C, Du Y, et al. Core-Shell Gold Nanorod@Metal-Organic Framework Nanoprobes for Multimodality Diagnosis of Glioma. Adv Mater. 2017;29(3):10.1002/adma.201604381. doi:10.1002/adma.201604381
6. Ji Z, Ai P, Shao C, et al. Manganese-doped carbon dots for magnetic resonance/optical dual-modal imaging of tiny brain glioma. ACS Biomaterials Science & Engineering. 2018;4(6):2089-2094. doi:10.1021/acsbiomaterials.7b01008
7. Yang Z, Du Y, Sun Q, et al. Albumin-based nanotheranostic probe with hypoxia alleviating potentiates synchronous multimodal imaging and Phototherapy for Glioma. ACS Nano. 2020;14(5):6191-6212. doi:10.1021/acsnano.0c02249
8. John F, Bosnyák E, Robinette NL, et al. Multimodal imaging-defined subregions in newly diagnosed glioblastoma: impact on overall survival. Neuro Oncol. 2019;21(2):264-273. doi:10.1093/neuonc/noy169