Photothermal immunotherapy of melanoma using TLR-7 agonist laden tobacco mosaic virus with polydopamine coat

Christian Isalomboto Nkanga; Oscar A Ortega-Rivera; Nicole F Steinmetz

doi:10.1016/j.nano.2022.102573

Photothermal immunotherapy of melanoma using TLR-7 agonist laden tobacco mosaic virus with polydopamine coat

Nanomedicine. 2022 Aug:44:102573. doi: 10.1016/j.nano.2022.102573. Epub 2022 Jun 18.

Authors

Christian Isalomboto Nkanga¹, Oscar A Ortega-Rivera², Nicole F Steinmetz³

Affiliations

¹ Department of NanoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States.
² Department of NanoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States; Center for Nano-ImmunoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States.
³ Department of NanoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States; Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States; Department of Radiology, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States; Center for Nano-ImmunoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States; Moores Cancer Center, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States; Institute for Materials Discovery and Design, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92039, United States. Electronic address: nsteinmetz@ucsd.edu.

Abstract

Photothermal therapy (PTT) is a promising cancer treatment that debulks tumors locally while priming immune responses. However, PTT as a standalone treatment approach often has limited systemic efficacy, motivating the development of synergistic combination approaches. Toward this goal, herein, the tobacco mosaic virus (TMV) was loaded with a small molecule immunomodulator, toll-like receptor 7 agonist (1V209), and its surface was coated with photothermal biopolymer polydopamine (PDA). The resulting 1V209-laden and PDA-coated TMV was used to treat B16F10 dermal melanoma in C57BL/6 mice. 1V209-TMV-PDA was intratumorally injected and irradiated using an 808-nm near infrared laser. 60 % of the mice receiving PTT with intratumoral 1V209-TMV-PDA + laser remained alive at the end point - in contrast to only 20 % survivors were observed in the control group. Immunological analysis indicates systemic anti-tumor immunity being induced by the combination therapy with a greater number of tumor-specific T cells (as determined by a splenocyte assay). This study highlights the potential of TMV versatility as a multifunctional nano-platform for combined PTT-immunotherapy.

Keywords: Anti-tumor immunotherapy; Melanoma; Nanoparticles; Photothermal therapy; Polydopamine; TLR-7 agonist; Tobacco mosaic virus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Animals
Cell Line, Tumor
Immunotherapy
Indoles
Melanoma*
Mice
Mice, Inbred C57BL
Nanoparticles*
Phototherapy
Polymers
Tobacco Mosaic Virus*
Toll-Like Receptor 7

Substances

Adjuvants, Immunologic
Indoles
Polymers
Toll-Like Receptor 7
polydopamine

Grants and funding

R01 CA202814/CA/NCI NIH HHS/United States