Original ArticleInduction of antitumor immunity in mice by the combination of nanoparticle-based photothermolysis and anti-PD-1 checkpoint inhibition
Graphical Abstract
In a poorly immunogenic syngeneic ovarian cancer model, short-pulsed wave (PW) laser photothermolysis based on near-infrared light-absorbing copper sulfide nanoparticles, combined with polymeric conjugate of the Toll-like receptor 9 agonist CpG and the immune checkpoint inhibitor anti-PD-1 antibody, significantly induced systemic immune response and prolonged mouse survival after re-inoculation of tumor cells at a distant site, compared to individual treatments alone.
Section snippets
Materials
Copper(II) chloride (CuCl2), sodium sulfide (Na2S·9H2O), PG, and methoxy-PEG-thiol (PEG-SH, molecular weight 5000) were purchased from Sigma-Aldrich (St. Louis, MO, USA). CpG oligonucleotide (ODC 2216) with 3′ terminal-amino group (5′-EEGGGACGATCGTCEEEEG-3′-NH2, CpG-3′-NH2) was purchased from Invitrogen (Chicago, IL, USA). Monoclonal anti-mouse PD-1 (CD279, clone: J43) was purchased from Bio X Cell (West Lebanon, NH, USA).
General procedure for the synthesis of PEGylated CuS NPs (PEG-CuS NPs)
For the synthesis of PEG-CuS NPs, 0.1 mL of sodium sulfide solution (Na2
Synthesis and characterization of PEGylated CuS NPs (PEG-CuS NPs)
The absorption spectrum of the PEG-CuS NPs in aqueous solution peaked at around 990 nm (Supplementary Figure S1, A). The mean hydrodynamic diameter of the PEG-CuS NPs was 25.6 nm measured by dynamic light scattering (Supplementary Figure S1, B). A transmission electron microscopy photograph of the PEG-CuS NPs is shown in Supplementary Figure S1, C; the mean diameter of PEG-CuS NPs measured in the dry state was 8.9 ± 3.0 nm. When PEG-CuS NPs of different concentrations (8 OD or 20 OD) were
Discussion
Findings from this study support the concept that the combination of PW laser-induced, NIR light-absorbing NP-mediated photothermolysis with immunotherapy (αPD-1 plus PG-CpG) can prolong the survival time of tumor-bearing mice.
One of the unique features of photothermolysis induced by short laser pulses is that it is highly spatially confined.10 Alternatively, a pulsed laser may be more efficient in generating immunogenic cell death because it can rapidly disrupt the cell membrane and thus may
Acknowledgments
The authors thank Ms. Stephanie P. Deming of Scientific Publications, Research Medical Library, MD Anderson Cancer Center, for editing the manuscript. We acknowledge that this work was supported in part by the John S. Dunn, Sr., Distinguished Chair in Diagnostic Imaging (Dr. William A. Murphy, Jr.) and by the University Cancer Foundation via the Institutional Research Grant program at The University of Texas MD Anderson Cancer Center. Additionally, A.K.S. was supported by grants P50 CA217685
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2022, Life SciencesCitation Excerpt :Furthermore, Yang, M. et al. demonstrated that CXCL13 potentiated the anti-PD-1 treatment response via the increase and stimulation of CXCR5+CD8+ T cells in subcutaneous ovarian cancer mouse model and the combination treatment significantly retarded tumor growth in mice [101]. Besides, it was showed that the combination of photothermolysis with immunotherapy [poly (L-glutamic acid) (PG)-CpG and anti-PD-1] significantly extended median survival time in ID8-ip1-Luc ovarian cancer mouse model and triggered durable response with memory T cells [102]. Thus, immune checkpoint blockade has immense potential in inducing tumor rejection significantly in ovarian cancer, which could be further maximized by boosting anti-tumor immune response with chemotherapy, small molecule inhibitors or vaccine.
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2022, Chemical Engineering JournalCitation Excerpt :Subcutaneous xenografts were convenient for experimental observation, and were easier and more widely available for preclinical research. Many preclinical studies on ovarian cancer have established subcutaneous xenograft models to simulate its effects and mechanisms [56–58]. Therefore, we chose to construct a subcutaneous xenograft model to evaluate the anti-tumor effect of constructed NPs.
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2022, Nanomedicine: Nanotechnology, Biology, and MedicineCitation Excerpt :Nanoparticles encapsulating adjuvants can prime and activate innate immune cells such as DCs in tandem with ICIs. These include TLR7 agonists such as imiquimod (R837)105 and resiquimod (R848),106 CpG (TLR9 agonist)107 and Vadimezan (STING) agonist).108 Nanoparticles such as dual-functioned maleimide polyethylene glycol-coated copper sulfide nanoparticles (CuS NPs-PEG-Mal) were also designed to serve as antigen traps.
Financial support: We acknowledge that this work was supported in part by the John S. Dunn, Sr., Distinguished Chair in Diagnostic Imaging (Dr. William A. Murphy, Jr.) and by the University Cancer Foundation via the Institutional Research Grant program at The University of Texas MD Anderson Cancer Center. Additionally, A.K.S. was supported by grants P50 CA217685 and R35 CA209904 from the National Cancer Institute; the American Cancer Society Research Professor Award; and the Frank McGraw Memorial Chair in Cancer Research. We acknowledge support by the NIH/NCI under award number P30CA016672 for the use of the High-Resolution Electron Microscopy, Flow Cytometry and Cellular Imaging, and Small Animal Imaging core facilities.
Competing interests: The authors have declared that no competing interest exists.
- 1
Current Address: Department of Radiology, The 1st Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
- 2
Current Address: The Second Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, China.
- 3
Current Address: Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.