Browsing by Author "Canning, Aidan J"

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    ItemOpen Access
    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, 2023-08) Srinivasan, Ethan S; Liu, Yang; Odion, Ren A; Chongsathidkiet, Pakawat; Wachsmuth, Lucas P; Haskell-Mendoza, Aden P; Edwards, Ryan M; Canning, Aidan J; Willoughby, Gavin; Hinton, Joseph; Norton, Stephen J; Lascola, Christopher D; Maccarini, Paolo F; Mariani, Christopher L; Vo-Dinh, Tuan; Fecci, Peter E

    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.
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    ItemOpen Access
    Xenorecognition and costimulation of porcine endothelium-derived extracellular vesicles in initiating human porcine-specific T cell immune responses.
    (American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2023-07) Li, Shu; Anwar, Imran J; Canning, Aidan J; Vo-Dinh, Tuan; Kirk, Allan D; Xu, He
    Porcine vascular endothelial cells (PECs) form a mechanistic centerpiece of xenograft rejection. Here, we determined that resting PECs release swine leukocyte antigen class I (SLA-I) but not swine leukocyte antigen class-II DR (SLA-DR) expressing extracellular vesicles (EVs) and investigated whether these EVs proficiently initiate xenoreactive T cell responses via direct xenorecognition and costimulation. Human T cells acquired SLA-I+ EVs with or without direct contact to PECs, and these EVs colocalized with T cell receptors. Although interferon gamma-activated PECs released SLA-DR+ EVs, the binding of SLA-DR+ EVs to T cells was sparse. Human T cells demonstrated low levels of proliferation without direct contact to PECs, but marked T cell proliferation was induced following exposure to EVs. EV-induced proliferation proceeded independent of monocytes/macrophages, suggesting that EVs delivered both a T cell receptor signal and costimulation. Costimulation blockade targeting B7, CD40L, or CD11a significantly reduced T cell proliferation to PEC-derived EVs. These findings indicate that endothelial-derived EVs can directly initiate T cell-mediated immune responses, and suggest that inhibiting the release of SLA-I EVs from organ xenografts has the potential to modify the xenograft rejection. We propose a secondary-direct pathway for T cell activation via xenoantigen recognition/costimulation by endothelial-derived EVs.