Plasmonic gold nanostars for synergistic photoimmunotherapy to treat cancer

Abstract

Cancer is the second leading cause of death and there is an urgent need to improve cancer management. We have developed an innovative cancer therapy named Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) by combining gold nanostars (GNS)-mediated photothermal ablation with checkpoint inhibitor immunotherapy. Our previous studies have demonstrated that SYMPHONY photoimmunotherapy not only treats the primary tumor but also dramatically amplifies anticancer immune responses in synergy with checkpoint blockade immunotherapy to treat remote and unresectable cancer metastasis. The SYMPHONY treatment also induces a 'cancer vaccine' effect leading to immunologic memory and prevents cancer recurrence in murine animal models. This manuscript provides an overview of our research activities on the SYMPHONY therapy with plasmonic GNS for cancer treatment.

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Citation

Published Version (Please cite this version)

10.1515/nanoph-2021-0237

Publication Info

Liu, Yang, Ericka Chorniak, Ren Odion, Wiguins Etienne, Smita K Nair, Paolo Maccarini, Gregory M Palmer, Brant A Inman, et al. (2021). Plasmonic gold nanostars for synergistic photoimmunotherapy to treat cancer. Nanophotonics, 10(12). pp. 3295–3302. 10.1515/nanoph-2021-0237 Retrieved from https://hdl.handle.net/10161/24170.

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Scholars@Duke

Nair

Smita K Nair

Professor in Surgery

I have 22 years of experience in the field of cancer vaccines and immunotherapy and I am an accomplished T cell immunologist. Laboratory website:
https://surgery.duke.edu/immunology-inflammation-immunotherapy-laboratory

Current projects in the Nair Laboratory:
1] Dendritic cell vaccines using tumor-antigen encoding RNA (mRNA, total tumor RNA, amplified tumor mRNA)
2] Local immune receptor modulation using mRNA that encodes for antibodies, receptor-ligands, cytokines, chemokines and toll-like receptors (current target list: CTLA4, GITR, PD1, TIM3, LAG3, OX40 and 41BB)
3] Combination therapies for cancer: cytotoxic therapy (radiation, chemo and oncolytic poliovirus therapy) with dendritic cell-based vaccines and immune checkpoint blockade
4] Adoptive T cell therapy using tumor RNA-transfected dendritic cells to expand tumor-specific T cells ex vivo
5] Adoptive T cell therapy using PSMA CAR (chimeric antigen receptor) RNA-transfected T cells
6] Direct injection of tumor antigen encoding RNA (targeting antigens to dendric cells in vivo using nanoparticles and aptamers)

Maccarini

Paolo F Maccarini

Associate Research Professor in the Department of Electrical and Computer Engineering
Palmer

Gregory M. Palmer

Professor of Radiation Oncology

Greg Palmer obtained his B.S. in Biomedical Engineering from Marquette University in 2000, after which he obtained his Ph.D. in BME from the University of Wisconsin, Madison. He is currently an Associate Professor in the Department of Radiation Oncology, Cancer Biology Division at Duke University Medical Center. His primary research focus has been identifying and exploiting the changes in absorption, scattering, and fluorescence properties of tissue associated with cancer progression and therapeutic response. To this end he has implemented a model-based approach for extracting absorber and scatterer properties from diffuse reflectance and fluorescence measurements. More recently he has developed quantitative imaging methodologies for intravital microscopy to characterize tumor functional and molecular response to radiation and chemotherapy. His awards have included the Jack Fowler Award from the Radiation Research Society.

Laboratory Website:
https://radonc.duke.edu/research-education/research-labs/radiation-and-cancer-biology/palmer-lab

Vo-Dinh

Tuan Vo-Dinh

R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering

Dr. Tuan Vo-Dinh is R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering, Professor of Chemistry, and Director of The Fitzpatrick Institute for Photonics.

Dr. Vo-Dinh’s research activities and interests involve biophotonics, nanophotonics, plasmonics, laser-excited luminescence spectroscopy, room temperature phosphorimetry, synchronous luminescence spectroscopy, and surface-enhanced Raman spectroscopy for multi-modality bioimaging, and theranostics (diagnostics and therapy) of diseases such as cancer and infectious diseases.

We have pioneered the development of a new generation of gene biosensing probes using surface-enhanced Raman scattering (SERS) detection with “Molecular Sentinels” and Plasmonic Coupling Interference (PCI) molecular probes for multiplex and label-free detection of nucleic acid biomarkers (DNA, mRNA, microRNA) in early detection of a wide variety of diseases.

In genomic and precision medicine, nucleic acid-based molecular diagnosis is of paramount importance with many advantages such as high specificity, high sensitivity, serotyping capability, and mutation detection. Using SERS-based plasmonic nanobiosensors and nanochips, we are developing novel nucleic acid detection methods that can be integrated into lab-on-a-chip systems for point-of-care diagnosis  (e.g., breast, GI cancer) and global health applications (e.g., detection of malaria and dengue).

In bioimaging, we are developing a novel multifunctional gold nanostar (GNS) probe for use in multi-modality bioimaging in pre-operative scans with PET, MRI and CT, intraoperative margin delineation with optical imaging, SERS and two-photon luminescence (TPL). The GNS can be used also for cancer treatment with plasmonics enhanced photothermal therapy (PTT), thus providing an excellent platform for seamless diagnostics and therapy (i.e., theranostics). Preclinical studies have shown its great potential for cancer diagnostics and therapeutics for future clinical translation.

For fundamental studies, various nanobiosensors are being developed for monitoring intracellular parameters (e.g., pH) and biomolecular processes (e.g., apoptosis, caspases), opening the possibility for fundamental molecular biological research as well as biomedical applications (e.g., drug discovery) at the single cell level in a systems biology approach. For point of care diagnostics, nanoprobes and nanochips with highly multiplex SERS detection and imaging use artificial intelligence and machine learning for data analysis.

Our research activities in immunotherapy involve unique plasmonics-active gold “nanostars.” These star-shaped nanobodies made of gold work like “lightning rods,” concentrating the electromagnetic energy at their tips and allowing them to capture photon energy more efficiently when irradiated by laser light. Teaming with medical collaborators, we have developed a novel cancer treatment modality, called synergistic immuno photothermal nanotherapy (SYMPHONY), which combines immune-checkpoint inhibition and gold nanostar–mediated photothermal immunotherapy that can unleash the immunotherapeutic efficacy of checkpoint inhibitors. This combination treatment can eradicate the primary tumors as well as distant “untreated” tumors, and induce immunologic memory like a “anti-cancer vaccine” effect in murine model.


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