Our group is tracking T cells and immune checkpoint receptors (ICRs) in vivo in real time with nanoparticle probes. Under normal physiological conditions, ICRs are crucial for the maintenance of self-tolerance. In tumors however, ICRs allow cancer cells to evade the antitumor immune response and proliferate. Particularly, the upregulation of programmed cell death protein-1 (PD-1) and binding of PD-1 to its ligand, PD-L1, impedes CD8+ T cell function contributing to immunosuppression. Whereas immunotherapies blocking PD-1/PD-L1 has been promising, >75% patients currently do not respond to these therapies. Current histopathologies are inadequate in assessing PD-L1 status, and PD-L1 screening alone cannot predict accurately patient response to therapies. It is imperative to dynamically detect multiple immunomarkers that are involved in immune modulation.
Each imaging modality has it merits and drawbacks; a single imaging technique cannot simultaneously achieve high sensitivity, specificity, depth-resolved resolution which requires us to seamlessly integrate multiple imaging modalities into a single platform. Our group is pursuing this goal by designing gold nanostars that can combine the abilities of positron emission tomography and surface enahcned Raman spectroscopy to both detect both PD-L1 positive tumor cells and CD8+ T cells, but also monitor response to immunotherapies in mouse models of cancer. The design of nanostars is versatile where the labels can be changed to allow other imaging modalities such as fluorescence or MRI. Further, this approach can be extended to numerous immune markers relevant in infectious diseases, neurodegenerative diseases, automimmunity etc.
Relevant Publications
Y-C. Ou, X. Wen, C. A. Johnson, D. Shae, O. Ayala, J. A. Webb, E. C. Lin, R. C. DeLapp, K. L. Boyd, M. Rafat, A. Richmond, A. Mahadevan-Jansen, J. T. Wilson, J. M. Balko, M. N. Tantawy, A. E. Vilgelm, R. Bardhan*, “Multimodal Multiplexed Immunoimaging with Nanostars for Detection of both PD-L1 and CD8, and Monitoring Response to Immunotherapies”, ACS Nano, under resubmission.
Y-C. Ou, X. Wen, R. Bardhan*, “Cancer Immunoimaging with Smart Nanoparticles”, Trends in Biotechnology, 2019, in press.
Y-C. Ou, J. A. Webb, C. M. O’Brien, I. Pence, E. C. Lin, E. P. Paul, D. Cole, S-H. Ou, M. Lapierre-Landry, E. S. Lippman, A. Mahadevan-Jansen, and R. Bardhan*, “Diagnosis of Immunomarkers in vivo via Multiplexed Surface Enhanced Raman Spectroscopy with Gold Nanostars “, Nanoscale, 2018, 10, 13092-13105
J. A. Webb#, Y-C. Ou#, S. Faley, E. P. Paul, J. P. Hittinger, C. C. Cutright, E. C. Lin, L. M. Bellan, and R. Bardhan*, “Theranostic Gold Nanoantennas for Simultaneous Multiplexed Raman Imaging of Immunomarkers and Photothermal Therapy”, ACS Omega, 2017, 2, 3583–3594. (# equal contributing first author).
J. A. Webb, and R. Bardhan*, “Emerging Advances in Nanomedicine with Engineered Gold Nanostructures” Invited Review, Nanoscale, 2014, 6, 2502-2530
W. Chen, C. Ayala-Orozco, N. C Biswal, C. Perez-Torres, M. Bartels, R. Bardhan, G. Stinnet, X.-De Liu, B. Ji, A. Deorukhkar, L. V Brown, S. Guha, R. G Pautler, S. Krishnan, N. J Halas, A. Joshi, “Targeting Pancreatic Cancer with Magneto-fluorescent Theranostic Gold Nanoshells”, Nanomedicine, 2014, 9, 1209-1222
R. Bardhan, S. Lal, A. Joshi, N. J. Halas, “Theranostic Nanoshells: from Probe Design to Imaging and Treatment of Cancer” , Invited, Accounts of Chemical Research, 2011, 44, 936–946
R. Bardhan, W. Chen, M. Bartels, C. Perez-Torres, M. F. Botero, R. W. McAninch, A. Contreras, R. Schiff, R. G. Pautler, N. J. Halas, A. Joshi, ” Tracking of multimodal therapeutic nanocomplexes targeting Breast Cancer in vivo” Nano Letters, 2010, 10, 4920–4928