Indocyanine green and poly I:C containing thermo-responsive liposomes used in immune-photothermal therapy prevent cancer growth and metastasis

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Abstract

Background

Efficient cancer therapy is sought not only for primary tumor treatment but also for the prevention of metastatic cancer growth. Immunotherapy has been shown to prevent cancer metastasis by inducing antigen-specific immune responses. Indocyanine green (ICG) has a peak spectral absorption at about 800 nm, which makes it a photothermal reagent for direct treatment of solid tumors by photothermal therapy (PTT). Since PTT alone cannot fully induce antigen-specific immune response for prevention of cancer metastasis, the combination of PTT and immunotherapy has been developed as a new strategy of cancer treatment.

Methods

Thermal responsive liposomes (TRL) were synthesized by incorporating ICG into the lipid bilayer and encapsulating the water-soluble immune stimulatory molecule polyinosinic:polycytidylic acid (poly I:C) in the hydrophilic core. The poly I:C- and ICG-containing TRLs (piTRLs) were analyzed according to size, and their photothermal effect was evaluated following laser irradiation at 808 nm. Moreover, the temperature-dependent release of poly I:C was also measured. For cancer therapy, CT-26 (carcinoma) and B16 (melanoma) cells were subcutaneously inoculated to build the 1st transplanted tumor in BALB/c and C57BL/6 mice, respectively. These mice received a 2nd transplantation with the same cancer cells by intravenous inoculation, for evaluation of the anti-metastatic effects of the liposomes after PTT.

Results

Near-infrared (NIR) laser irradiation increased the temperature of piTRLs and effectively released poly I:C from the liposomes. The increased temperature induced a photothermal effect, which promoted cancer cell apoptosis and dissolution of the 1st transplanted tumor. Moreover, the released poly I:C from the piTRL induced activation of dendritic cells (DCs) in tumor draining lymph node (tdLN). Cancer cell apoptosis and DC-activation-mediated cancer antigen-specific immune responses further prevented growth of lung metastatic cancer developed following intravenous transplantation of cancer cells.

Conclusion

These results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases.

Electronic supplementary material

The online version of this article (10.1186/s40425-019-0702-1) contains supplementary material, which is available to authorized users.

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Most cited references 29

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Therapeutic developments in pancreatic cancer: current and future perspectives

John Neoptolemos, William Greenhalf, Jörg Kleeff … (2018)

The overall 5-year survival for pancreatic cancer has changed little over the past few decades, and pancreatic cancer is predicted to be the second leading cause of cancer-related mortality in the next decade in Western countries. The past few years, however, have seen improvements in first-line and second-line palliative therapies and considerable progress in increasing survival with adjuvant treatment. The use of biomarkers to help define treatment and the potential of neoadjuvant therapies also offer opportunities to improve outcomes. This Review brings together information on achievements to date, what is working currently and where successes are likely to be achieved in the future. Furthermore, we address the questions of how we should approach the development of pancreatic cancer treatments, including those for patients with metastatic, locally advanced and borderline resectable pancreatic cancer, as well as for patients with resected tumours. In addition to embracing newer strategies comprising genomics, stromal therapies and immunotherapies, conventional approaches using chemotherapy and radiotherapy still offer considerable prospects for greater traction and synergy with evolving concepts.

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Elucidating the fundamental mechanisms of cell death triggered by photothermal therapy.

Jilian R Melamed, Rachel S. Edelstein, Emily S Day (2015)

Photothermal therapy (PTT) utilizes nanoparticles embedded within tumors as exogenous energy absorbers to convert laser light energy into heat to ablate cancer cells. While PTT is a promising alternative to conventional cancer therapy, under certain irradiation conditions, it can produce cellular necrosis, and this necrosis may lead to pro-inflammatory responses that are detrimental to treatment success. Recent studies have shown that PTT can be modulated to induce apoptosis rather than necrosis, which is appealing since apoptosis discourages an inflammatory response. In this issue of ACS Nano, del Pino, Pardo, de la Fuente, and colleagues reveal the intracellular signaling cascades involved in the apoptotic response to PTT using cells harboring photothermal transducing nanoprisms. In this Perspective, we present an overview of nanoparticle-mediated PTT and discuss photothermally induced apoptosis as a potential therapeutic pathway.

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The promise and challenges of immune agonist antibody development in cancer

Axel Hoos, Kenneth Hance, Patrick Mayes (2018)

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Author and article information

Contributors

Jun-O Jin:

ORCID: http://orcid.org/0000-0003-4216-8111

82-53-810-3033 , jinjo@yu.ac.kr

Journal

Journal ID (nlm-ta): J Immunother Cancer

Journal ID (iso-abbrev): J Immunother Cancer

Title: Journal for Immunotherapy of Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 2051-1426

Publication date (Electronic): 14 August 2019

Publication date PMC-release: 14 August 2019

Publication date Collection: 2019

Volume: 7

Electronic Location Identifier: 220

Affiliations

[1 ]ISNI 0000 0001 0125 2443, GRID grid.8547.e, Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Shanghai Medical College, , Fudan University, ; Shanghai, 201508 China

[2 ]ISNI 0000 0001 0674 4447, GRID grid.413028.c, Department of Medical Biotechnology, , Yeungnam University, ; Gyeongsan, 38541 South Korea

[3 ]ISNI 0000 0001 0719 8994, GRID grid.412576.3, Department of Chemistry, , Pukyong National University, ; Busan, 48513 South Korea

[4 ]ISNI 0000 0001 0719 8994, GRID grid.412576.3, Marine-Integrated Bionics Research Center, , Pukyong National University, ; Busan, 48513 South Korea

[5 ]ISNI 0000 0001 0719 8994, GRID grid.412576.3, Department of Biomedical Engineering and Center for Marine-Integrated Biomedical Technology (BK21 Plus), , Pukyong National University, ; Busan, 48513 South Korea

[6 ]ISNI 0000 0001 0719 8994, GRID grid.412576.3, Interdisciplinary Program of Biomedical Mechanical & Electrical Engineering, , Pukyong National University, ; Busan, 48513 South Korea

[7 ]ISNI 0000 0001 0842 2126, GRID grid.413967.e, Department of Biomedical Sciences, , University of Ulsan College of Medicine, ASAN Medical Center, ; Seoul, South Korea

Author information

Jun-O Jin http://orcid.org/0000-0003-4216-8111

Article

Publisher ID: 702

DOI: 10.1186/s40425-019-0702-1

PMC ID: 6694491

PubMed ID: 31412934

SO-VID: f23591b9-7f24-4ded-8580-4c3d732e6f7b

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 14 February 2019

Date accepted : 31 July 2019

Funding

Funded by: National Research Foundation of Korea

Award ID: NRF-2019R1C1C1003334

Award Recipient : Jun-O Jin

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81600869

Award Recipient : Wei Zhang

Custom metadata

Keywords: liposome,indocyanine green,polyinosinic:polycytidylic acid,photothermal therapy,immunotherapy,anti-metastasis

Data availability:

Keywords: liposome, indocyanine green, polyinosinic:polycytidylic acid, photothermal therapy, immunotherapy, anti-metastasis

Indocyanine green and poly I:C containing thermo-responsive liposomes used in immune-photothermal therapy prevent cancer growth and metastasis

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Abstract

Background

Methods

Results

Conclusion

Electronic supplementary material

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Cancer Immunotherapy

Most cited references 29

Therapeutic developments in pancreatic cancer: current and future perspectives

Elucidating the fundamental mechanisms of cell death triggered by photothermal therapy.

The promise and challenges of immune agonist antibody development in cancer

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Contributors

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