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In vivo imaging of T cells loaded with gold nanoparticles: a pilot study

  • Molecular Imaging
  • Published:
La radiologia medica Aims and scope Submit manuscript

Abstract

Purpose

Malignant tumours develop strategies to avoid immune recognition and elimination by T cells, even in individuals with a fully functioning immune system. To explore the treatment approach of adoptive immunotherapy, we exploited T cells loaded with radiolabelled gold nanoparticles (AuNPs) to track T cells in vivo.

Materials and methods

Surface-modified AuNPs were radiolabelled with 111In or 64Cu. They were then transferred into T cells via electroporation. To evaluate the effectiveness of this process, T cells loaded with 111In-radiolabelled AuNPs were injected directly into the right lung of nude mice for in vivo imaging by micro-SPECT/CT. T cells loaded with 64Cu-radiolabelled AuNPs were then injected into the tail vein of nude mice and imaged by micro-PET/CT.

Results

High uptake signals were observed in the right lung following the direct injection of T cells containing 111In-labelled AuNPs. Imaging showed a marked difference in the dynamic biodistribution of T cells containing 64Cu-labelled AuNPs when compared with 64Cu-labelled AuNPs alone.

Conclusions

This study demonstrated the feasibility of the in vivo imaging of T cells loaded with radiolabelled AuNPs.

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References

  1. Cao S, Wang YL, Ren XB et al (2011) Efficacy of large doses of IL-2-activated human leukocyte antigen haploidentical peripheral blood stem cells on refractory metastatic renal cell carcinoma. Cancer Biother Radiopharm 26:503–510

    Article  PubMed  CAS  Google Scholar 

  2. Sau TK, Murphy CJ (2004) Seeded high yield synthesis of short Au nanorods in aqueous solution. Langmuir 20:6414–6420

    Article  PubMed  CAS  Google Scholar 

  3. Dossett ML, Teague RM, Schmitt TM et al (2009) Adoptive immunotherapy of disseminated leukemia with TCR-transduced, CD8+ T cells expressing a known endogenous TCR. Mol Ther 17:742–749

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Urbanska K, Lanitis E, Poussin M et al (2012) A universal strategy for adoptive immunotherapy of cancer through use of a novel T cell antigen receptor. Cancer Res 72:1844–1852

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Al-Khami AA, Mehrotra S, Nishimura MI (2011) Adoptive immunotherapy of cancer: gene transfer of T cell specificity. Self Nonself 2:80–84

    Article  PubMed Central  PubMed  Google Scholar 

  6. Jin Z, Maiti S, Huls H et al (2011) The hyperactive Sleeping Beauty transposase SB100X improves the genetic modification of T cells to express a chimeric antigen receptor. Gene Ther 18:849–856

    Article  PubMed  CAS  Google Scholar 

  7. Yeh TC, Zhang W, Ildstad ST et al (1995) In vivo dynamic MRI tracking of rat T-cells labeled with superparamagnetic iron-oxideparticles. Magn Reson Med 33:200–208

    Article  PubMed  CAS  Google Scholar 

  8. Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5:161–171

    Article  PubMed  CAS  Google Scholar 

  9. Vasudev SS, Ahmad S, Parveen R et al (2011) Formulation of PEG-ylated L-asparaginase loaded poly (lactide-co-glycolide) nanoparticles: influence of PEGylation on enzyme loading, activity and in vitro release. Pharmazie 66:956–960

    PubMed  CAS  Google Scholar 

  10. Jain S, Hirst DG, O’Sullivan JM (2012) Gold nanoparticles as novel agents for cancer therapy. Br J Radiol 85:101–113

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. El-Dakdouki MH, Zhu DC, El-Boubbou K et al (2012) Development of multifunctional hyaluronan-coated nanoparticles for imaging and drug delivery to cancer cells. Biomacromolecules 13:1144–1151

    Article  PubMed  CAS  Google Scholar 

  12. Xie H, Wang ZJ, Bao A et al (2010) In vivo PET imaging and biodistribution of radiolabeled gold nanoshells in rats with tumor xenografts. Int J Pharm 395:324–330

    Article  PubMed  CAS  Google Scholar 

  13. Patra CR, Bhattacharya R, Mukhopadhyay D et al (2010) Fabrication of gold nanoparticles for targeted therapy in pancreatic cancer. Adv Drug Deliv Rev 62:346–361

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60:1615–1626

    Article  PubMed  CAS  Google Scholar 

  15. Loo C, Lowery A, Halas N et al (2005) Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5:709–711

    Article  PubMed  CAS  Google Scholar 

  16. Lowery AR, Gobin AM, Day ES (2006) Immunonanoshells for targeted photothermal ablation of tumor cells. Int J Nanomed 1:149–154

    Article  CAS  Google Scholar 

  17. Xie H, Gill-Sharp KL, O’Neal DP (2007) Quantitative estimation of gold nanoshell concentration in whole blood using dynamic light scattering. Nanomedicine 3:89–94

    Article  PubMed  CAS  Google Scholar 

  18. Zhao Y, Moon E, Carpenito C et al (2010) Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res 70:9053–9061

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Lu W, Zhang G, Zhang R et al (2010) Tumor site-specific silencing of NF-kappaB p65 by targeted hollow gold nanosphere-mediated photothermal transfection. Cancer Res 70:3177–3188

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Zhou X, Zhang X, Yu X et al (2008) The effect of conjugation to gold nanoparticles on the ability of low molecular weight chitosan to transfer DNA vaccine. Biomaterials 29:111–117

    Article  PubMed  CAS  Google Scholar 

  21. Ballester M, Nembrini C, Dhar N et al (2011) Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis. Vaccine 29:6959–6966

    Article  PubMed  CAS  Google Scholar 

  22. Van Tendeloo VF, Willems R, Ponsaerts P et al (2000) High-level transgene expression in primary human T lymphocytes and adult bone marrow CD34+ cells via electroporation-mediated gene delivery. Gene Ther 7:1431–1437

    Article  PubMed  CAS  Google Scholar 

  23. Arnaud-Cormos D, Leveque P, Wu YH et al (2011) Microchamber setup characterization for nanosecond pulsed electric field exposure. IEEE Trans Biomed Eng 58:1656–1662

    Article  PubMed  Google Scholar 

  24. Jordan ET, Collins M, Terefe J et al (2008) Optimizing electroporation conditions in primary and other difficult-to-transfect cells. J Biomol Tech 19:328–334

    PubMed Central  PubMed  Google Scholar 

  25. Bhattacharya A, Turowski SG, San Martin ID et al (2011) Magnetic resonance and fluorescence-protein imaging of the anti-angiogenic and anti-tumor efficacy of selenium in an orthotopic model of human colon cancer. Anticancer Res 31:387–393

    PubMed Central  PubMed  CAS  Google Scholar 

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Acknowledgments

This research was supported by NSFC 81271540/H1801 and STCSM 10411953500.

Conflict of interest

Hui Li, Laura Diaz, Daniel Lee, Lei Cui, Xin Liang, Yingsheng Cheng, declare no conflict of interest.

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Correspondence to Yingsheng Cheng.

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11547_2013_335_MOESM1_ESM.tif

TEM images of AuNPs under two different experimental conditions. a) AuNPs without electroporation; b) AuNPs after electroporation (TIFF 180 kb)

11547_2013_335_MOESM2_ESM.tif

DLS data of the AuNPs of two different experimental conditions: a) AuNPs without electroporation; b) AuNPs after electroporation. Blue bar: particle size distribution of the AuNP core; red bar: particle size distribution of AuNPs (TIFF 59 kb)

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Li, H., Diaz, L., Lee, D. et al. In vivo imaging of T cells loaded with gold nanoparticles: a pilot study. Radiol med 119, 269–276 (2014). https://doi.org/10.1007/s11547-013-0335-2

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  • DOI: https://doi.org/10.1007/s11547-013-0335-2

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