Skip to main content
Log in

Exosome-modified PLGA Microspheres for Improved Internalization into Dendritic Cells and Macrophages

  • Research Paper
  • Nanobiotechnology
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

Considering the significance of effective antigen presentation for boosting immune responses, it is essential to develop delivery systems for antigen presenting cells (APCs; dendritic cells and macrophages). As a simple and facile way for improving delivery efficiency of PLGA microspheres (MS) into APCs, we fabricated exosome-conjugated PLGA MS via polydopamine coating in this study. Spherical micro-sized particles were first prepared by conventional water-in oil-in water (W1/O/W2) double emulsion and solvent evaporation methods and were observed by scanning electron microscopy (SEM). With increasing model protein (ovalbumin)/MS weight ratios, higher amounts of ovalbumin (OVA) were immobilized onto MS. After exosome (EXO) conjugation to MS via polydopamine coating, the amount of nitrogen was significantly increased on the surface of MS, indicating that EXO were successfully conjugated onto MS. EXO-coated dopamine MS (EXO-Dopa MS) exhibited significantly improved delivery into DC2.4 cells and RAW264.7 cells, compared with bare MS and Dopa MS. Therefore, EXO-Dopa MS could be used as effective carriers of immune stimulating biomolecules into APCs for cancer immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Mann, E. R. and X. Li (2014) Intestinal antigen-presenting cells in mucosal immune homeostasis: crosstalk between dendritic cells, macrophages and B-cells. World J. Gastroenterol. 20: 9653–9664.

    Article  Google Scholar 

  2. Kambayashi, T. and T. M. Laufer (2014) Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell? Nat. Rev. Immunol. 14: 719–730.

    Article  CAS  Google Scholar 

  3. Liu, Q., J. Jia, T. Yang, Q. Fan, L. Wang, and G. Ma (2016) Pathogen-mimicking polymeric nanoparticles based on dopamine polymerization as vaccines adjuvants induce robust humoral and cellular immune responses. Small. 12: 1744–1757.

    Article  CAS  Google Scholar 

  4. Hwang, J., K. Lee, A. A. Gilad, and J. Choi (2018) Synthesis of Beta-glucan nanoparticles for the delivery of single strand DNA. Biotechnol. Bioprocess Eng. 23: 144–149.

    Article  CAS  Google Scholar 

  5. Hao, S., Y. Yan, X. Ren, Y. Xu, L. Chen, and H. Zhang (2015) Candesartan-graft-polyethyleneimine cationic micelles for effective co-delivery of drug and gene in anti-angiogenic lung cancer therapy. Biotechnol. Bioprocess Eng. 20: 550–560.

    Article  CAS  Google Scholar 

  6. Brannon-Peppas, L. and J. O. Blanchette (2004) Nanoparticle and targeted systems for cancer therapy. Adv. Drug Deliv. Rev. 56: 1649–1659.

    Article  CAS  Google Scholar 

  7. Liang, X., J. Duan, X. Li, X. Zhu, Y. Chen, X. Wang, H. Sun, D. Kong, C. Li, and J. Yang (2018) Improved vaccine-induced immune responses via a ROS-triggered nanoparticle-based antigen delivery system. Nanoscale. 10: 9489–9503.

    Article  CAS  Google Scholar 

  8. Foged, C., B. Brodin, S. Frokjaer, and A. Sundblad (2005) Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int. J. Pharm. 298: 315–322.

    Article  CAS  Google Scholar 

  9. Liu, Y., Y. Yin, L. Wang, W. Zhang, X. Chen, X. Yang, J. Xu, and G. Ma (2013) Surface hydrophobicity of microparticles modulates adjuvanticity. J. Mater. Chem. B. 1: 3888–3896.

    Article  CAS  Google Scholar 

  10. Sharma, G., D. T. Valenta, Y. Altman, S. Harvey, H. Xie, S. Mitragotri, and J. W. Smith (2010) Polymer particle shape independently influences binding and internalization by macrophages. J. Control Release. 147: 408–412.

    Article  CAS  Google Scholar 

  11. Champion, J. A., A. Walker, and S. Mitragotri (2008) Role of particle size in phagocytosis of polymeric microspheres. Pharm. Res. 25: 1815–1821.

    Article  CAS  Google Scholar 

  12. Niu, Y., M. Yu, S. B. Hartono, J. Yang, H. Xu, H. Zhang, J. Zhang, J. Zou, A. Dexter, W. Gu, and C. Yu (2013) Nanoparticles mimicking viral surface topography for enhanced cellular delivery. Adv. Mater. 25: 6233–6237.

    Article  CAS  Google Scholar 

  13. Jung, H., H. E. Jang, Y. Y. Kang, J. Song, and H. Mok (2019) PLGA microspheres coated with cancer cell-derived vesicles for improved internalization into antigen-presenting cells and immune stimulation. Bioconjug. Chem. 30: 1690–1701.

    Article  CAS  Google Scholar 

  14. van Niel, G., G. D’Angelo, and G. Raposo (2018) Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19: 213–228.

    Article  CAS  Google Scholar 

  15. Zhang, M., X. Zang, M. Wang, Z. Li, M. Qiao, H. Hu, and D. Chen (2019) Exosome-based nanocarriers as bio-inspired and versatile vehicles for drug delivery: recent advances and challenges. J. Mater. Chem. B. 7: 2421–2433.

    Article  CAS  Google Scholar 

  16. Yu, G., H. Jung, Y. Y. Kang, and H. Mok (2018) Comparative evaluation of cell- and serum-derived exosomes to deliver immune stimulators to lymph nodes. Biomaterials. 162: 71–81.

    Article  CAS  Google Scholar 

  17. Pozzi, L. A. M., J. W. Maciaszek, and K. L. Rock (2005) Both dendritic cells and macrophages can stimulate naive CD8 T cells in vivo to proliferate, develop effector function, and differentiate into memory cells. J. Immunol. 175: 2071–2081.

    Article  CAS  Google Scholar 

  18. Choi, E. S., Y. Y. Kang, and H. Mok (2018) Evaluation of the enhanced antioxidant activity of curcumin within exosomes by fluorescence monitoring. Biotechnol. Bioprocess Eng. 23: 150–157.

    Article  CAS  Google Scholar 

  19. Jang, H. E. and H. Mok (2016) Polydopamine-coated porous microspheres conjugated with immune stimulators for enhanced cytokine induction in macrophages. Macromol. Biosci. 16: 1562–1569.

    Article  CAS  Google Scholar 

  20. Lee, H., S. M. Dellatore, W. M. Miller, and P. B. Messersmith (2007) Mussel-inspired surface chemistry for multifunctional coatings. Science. 318: 426–430.

    Article  CAS  Google Scholar 

  21. Lee, E., H. E. Jang, Y. Y. Kang, J. Kim, J. H. Ahn, and H. Mok (2016) Submicron-sized hydrogels incorporating cyclic dinucleotides for selective delivery and elevated cytokine release in macrophages. Acta Biomater. 29: 271–281.

    Article  CAS  Google Scholar 

  22. San Roman, B., S. Gomez, J. M. Irache, and S. Espuelas (2014) Co-encapsulated CpG oligodeoxynucleotides and ovalbumin in PLGA microparticles; an in vitro and in vivo study. J. Pharm. Pharm. Sci. 17: 541–553.

    Article  CAS  Google Scholar 

  23. Monkare, J., M. Pontier, E. E. M. van Kampen, G. Du, M. Leone, S. Romeijn, M. R. Nejadnik, C. O’Mahony, B. Slütter, W. Jiskoot, and J. A. Bouwstra (2018) Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery. Eur. J. Pharm. Biopharm. 129: 111–121.

    Article  Google Scholar 

  24. Soung, Y. H., S. Ford, V. Zhang, and J. Chung (2017) Exosomes in cancer diagnostics. Cancers (Basel). 9: 8–18.

    Article  Google Scholar 

  25. Le-Masurier, S. P., H. T. T. Duong, C. Boyer, and A. M. Granville (2015) Surface modification of polydopamine coated particles via glycopolymer brush synthesis for protein binding and FLIM testing. Polym. Chem. 6: 2504–2511.

    Article  CAS  Google Scholar 

  26. Valitutti, S., D. Coombs, and L. Dupre (2010) The space and time frames of T cell activation at the immunological synapse. FEBS Lett. 584: 4851–4857.

    Article  CAS  Google Scholar 

  27. Sprent, J. (2005) Direct stimulation of naive T cells by antigen-presenting cell vesicles. Blood Cells Mol. Dis. 35: 17–20.

    Article  CAS  Google Scholar 

  28. Wang, J., J. Li, and J. Ren (2019) Surface modification of poly(lactic-co-glycolic acid) microspheres with enhanced hydrophilicity and dispersibility for arterial embolization. Materials (Basel). 12: 1959–1969.

    Article  CAS  Google Scholar 

  29. Kao, C. T., C. C. Lin, Y. W. Chen, C. H. Yeh, H. Y. Fang, and M. Y. Shie (2015) Poly(dopamine) coating of 3D printed poly(lactic acid) scaffolds for bone tissue engineering. Mater. Sci. Eng. C. Mater Biol Appl. 56: 165–173.

    Article  CAS  Google Scholar 

  30. Chen, J., Q. Li, J. Xu, L. Zhang, M. F. Maitz, and J. Li (2015) Thromboresistant and rapid-endothelialization effects of dopamine and staphylococcal protein A mediated anti-CD34 coating on 316L stainless steel for cardiovascular devices. J Mater Chem B. 3: 2615–2623.

    Article  CAS  Google Scholar 

  31. Cai, H., X. Wen, L. Wen, N. Tirelli, X. Zhang, Y. Zhang, H. Su, F. Yang, and G. Chen (2014) Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration. Int. J. Nanomed. 9: 5591–5601.

    Article  Google Scholar 

  32. Lee, S. S., Y. B. Lee, and I. J. Oh (2015) Cellular uptake of poly(DL-lactide-co-glycolide) nanoparticles: effects of drugs and surface characteristics of nanoparticles. J. Pharm. Investig. 45: 659–667.

    Article  CAS  Google Scholar 

  33. Santos, P. M. and L. H. Butterfield (2018) Dendritic cell-based cancer vaccines. J. Immunol. 200: 443–449.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This paper was supported by Konkuk University in 2019. The authors declare no conflict of interest.

Neither ethical approval nor informed consent was required for this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hyejung Mok.

Additional information

Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary materials

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

You, G., Kim, Y., Lee, J.H. et al. Exosome-modified PLGA Microspheres for Improved Internalization into Dendritic Cells and Macrophages. Biotechnol Bioproc E 25, 521–527 (2020). https://doi.org/10.1007/s12257-020-0008-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-020-0008-7

Keywords

Navigation