Gold Nanostars Obviate Limitations to Laser Interstitial Thermal Therapy (LITT) for the Treatment of Intracranial Tumors.
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2023-08
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Abstract
Purpose
Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT.Experimental design
The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel-based phantoms of control and GNS-infused central "tumors." In vivo accumulation of GNS and amplification of ablation were tested in murine intracranial and extracranial tumor models followed by intravenous GNS injection, PET/CT, two-photon photoluminescence, inductively coupled plasma mass spectrometry (ICP-MS), histopathology, and laser ablation.Results
Monte Carlo simulations demonstrated the potential of GNS to accelerate and specify thermal distributions. In ex vivo cuboid tumor phantoms, the GNS-infused phantom heated 5.5× faster than the control. In a split-cylinder tumor phantom, the GNS-infused border heated 2× faster and the surrounding area was exposed to 30% lower temperatures, with margin conformation observed in a model of irregular GNS distribution. In vivo, GNS preferentially accumulated within intracranial tumors on PET/CT, two-photon photoluminescence, and ICP-MS at 24 and 72 hours and significantly expedited and increased the maximal temperature achieved in laser ablation compared with control.Conclusions
Our results provide evidence for use of GNS to improve the efficiency and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors and amplification of laser ablation, and the GNS-infused phantom experiments demonstrate increased rates of heating, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.Type
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Srinivasan, Ethan S, Yang Liu, Ren A Odion, Pakawat Chongsathidkiet, Lucas P Wachsmuth, Aden P Haskell-Mendoza, Ryan M Edwards, Aidan J Canning, et al. (2023). Gold Nanostars Obviate Limitations to Laser Interstitial Thermal Therapy (LITT) for the Treatment of Intracranial Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research, 29(16). pp. 3214–3224. 10.1158/1078-0432.ccr-22-1871 Retrieved from https://hdl.handle.net/10161/28960.
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Scholars@Duke
Aidan Canning
Christopher David Lascola
Paolo F Maccarini
Peter Edward Fecci
As the Director of both the Brain Tumor Immunotherapy Program and the Center for Brain and Spine Metastasis at Duke University, I focus our programmatic interests on the design, optimization, and monitoring of immune-based treatment platforms for patients with intracranial tumors, whether primary or metastatic. Within this broad scope, however, my own group looks more specifically at limitations to immunotherapeutic success, with a particular focus on understanding and reversing T cell dysfunction in patients with glioblastoma (GBM) and brain metastases. We employ a systematic approach to categorizing T cell dysfunction (Woroniecka et al, Clin Cancer Res 2018 Aug 15;24(16):3792-3802), and whereas our earlier work addressed concerns for regulatory T cell-induced tolerance, we now heavily study T cell ignorance and exhaustion, as well. Regarding the former, we recently published the novel phenomenon of S1P1-mediated bone marrow T cell sequestration in patients with intracranial tumors (Chongsathidkiet et al, Nat Medicine 2018 Sep;24(9):1459-1468). Regarding the latter, we have likewise recently identified and characterized exhaustion as a significant limitation to T-cell function within GBM (Woroniecka et al, Clin Cancer Res 2018 Sep 1;24(17):4175-4186). I very much look to collaboratively integrate our approaches with others investigating innovative treatment options. I continue my focus on combining strategies for reversing T cell deficits with current and novel immune-based platforms as a means of deriving and improving rational and precise anti-tumor therapies. It is my sincerest desire to forge a career focused on co-operative, multi-disciplinary, organized brain tumor therapy. Ultimately, my goal is to help coordinate the efforts of a streamlined and effective center for brain tumor research and clinical care. I hope to play some role in ushering in a period where the science and treatment arms of brain tumor therapy suffer no disjoint, but instead represent the convergent efforts of researchers, neuro-oncologists, medical oncologists, radiation oncologists, biomedical engineers, and neurosurgeons alike. I hope to see such synergy become standard of care.
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