Shortwave-infrared-light-emitting probes for the in vivo tracking of cancer vaccines and the elicited immune responses

Fuqiang Ren; Feifei Wang; Ani Baghdasaryan; Ying Li; Haoran Liu; RuSiou Hsu; Chuchu Wang; Jiachen Li; Yeteng Zhong; Felix Salazar; Chun Xu; Yingying Jiang; Zhuoran Ma; Guanzhou Zhu; Xiang Zhao; Kerry Kaili Wong; Richard Willis; K Christopher Garcia; Anna Wu; Elizabeth Mellins; Hongjie Dai

doi:10.1038/s41551-023-01083-5

Shortwave-infrared-light-emitting probes for the in vivo tracking of cancer vaccines and the elicited immune responses

Nat Biomed Eng. 2023 Aug 24. doi: 10.1038/s41551-023-01083-5. Online ahead of print.

Authors

Fuqiang Ren^#¹, Feifei Wang^#¹, Ani Baghdasaryan^#¹, Ying Li², Haoran Liu¹, RuSiou Hsu¹, Chuchu Wang^{3

4}, Jiachen Li¹, Yeteng Zhong¹, Felix Salazar⁵, Chun Xu¹, Yingying Jiang¹, Zhuoran Ma¹, Guanzhou Zhu¹, Xiang Zhao⁶, Kerry Kaili Wong², Richard Willis⁷, K Christopher Garcia⁶, Anna Wu⁵, Elizabeth Mellins², Hongjie Dai⁸

Affiliations

¹ Department of Chemistry and Bio-X, Stanford University, Stanford, CA, USA.
² Department of Pediatrics, Human Gene Therapy, Stanford University, Stanford, CA, USA.
³ Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
⁴ Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
⁵ Department of Radiation Oncology, City of Hope, CA, USA.
⁶ Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
⁷ NIH Tetramer Facility at Emory Vaccine Center, Emory University, Atlanta, GA, USA.
⁸ Department of Chemistry and Bio-X, Stanford University, Stanford, CA, USA. hdai1@stanford.edu.

^# Contributed equally.

PMID: 37620621
DOI: 10.1038/s41551-023-01083-5

Abstract

Tracking and imaging immune cells in vivo non-invasively would offer insights into the immune responses induced by vaccination. Here we report a cancer vaccine consisting of polymer-coated NaErF₄/NaYF₄ core-shell down-conversion nanoparticles emitting luminescence in the near-infrared spectral window IIb (1,500-1,700 nm in wavelength) and with surface-conjugated antigen (ovalbumin) and electrostatically complexed adjuvant (class-B cytosine-phosphate-guanine). Whole-body wide-field imaging of the subcutaneously injected vaccine in tumour-bearing mice revealed rapid migration of the nanoparticles to lymph nodes through lymphatic vessels, with two doses of the vaccine leading to the complete eradication of pre-existing tumours and to the prophylactic inhibition of tumour growth. The abundance of antigen-specific CD8⁺ T lymphocytes in the tumour microenvironment correlated with vaccine efficacy, as we show via continuous-wave imaging and lifetime imaging of two intravenously injected near-infrared-emitting probes (CD8⁺-T-cell-targeted NaYbF₄/NaYF₄ nanoparticles and H-2K^b/ovalbumin_257-264 tetramer/PbS/CdS quantum dots) excited at different wavelengths, and by volumetrically visualizing the three nanoparticles via light-sheet microscopy with structured illumination. Nanoparticle-based vaccines and imaging probes emitting infrared light may facilitate the design and optimization of immunotherapies.