Programmable Membrane-Mediated Attachment of Synthetic Virus-like Nanoparticles on Artificial Protocells for Enhanced Immunogenicity

Vincent Mukwaya, Peipei Zhang, Lingshan Liu, Auphedeous Yinme Dang-i, Mei Li, Stephen Mann*, Hongjing Dou

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

The programming of protocells to implement and control the functions of living cells through activated membrane receptor signaling remains a challenge for the development of protoliving technologies. Here, we report a synthetic protocell capable of inducing high levels of macrophage activation in vitro. An immunogenic protocell comprising hyaluronic acid (HA)-polymer membrane decorated with synthetic virus-like particles derived from the functionalization of core-shell polymer nanoparticles with a Toll-like receptor agonist (Pam3SK4) and cell/protocell membrane-binding lectin (WGA) is fabricated. While the non-decorated HA-based protocells and functionalized SVLPs alone initiate moderate levels of macrophage activation, co-presentation of WGA and Pam3SK4 on the protocell membrane results in hyperactivation of the phagocytes via a synergistic multi-receptor process. This work offers opportunities for developing chemically programmable soft microscale agents capable of eliciting cellular signal transduction and genetic outputs and provides a step toward implementing future therapeutic strategies based on cognate interactions at the cell-protocell interface.

Original languageEnglish
Article number100291
JournalCell Reports Physical Science
Volume2
Issue number1
DOIs
Publication statusPublished - 20 Jan 2021

Bibliographical note

Funding Information:
We wish to gratefully acknowledge financial support from the National Natural Science Foundation of China ( 21871180 ), the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning ( SHDP201802 ), the “Shuguang Program” supported by the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission ( 17SG12 ), the Science and Technology Commission of Shanghai Municipality ( 18520710300 and 17ZR1404100 ), Biomedical Interdisciplinary Research Foundation of SJTU ( YG2019QNB34 ), and EU Horizon 2020 (Advanced Grant Scheme 740235 ). The authors are grateful to the Instrumental Analysis Centre of the SJTU for their assistance with material characterization and qPCR. The authors thank Prof. Rubing Liang at the School of Life Sciences of SJTU for providing facilities for cDNA synthesis and Prof. Xin Huang at the Harbin Institute of Technology for suggestions for the synthesis of the mercaptothiazoline-capped RAFT agent.

Funding Information:
We wish to gratefully acknowledge financial support from the National Natural Science Foundation of China (21871180), the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (SHDP201802), the ?Shuguang Program? supported by the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission ( 17SG12), the Science and Technology Commission of Shanghai Municipality (18520710300 and 17ZR1404100), Biomedical Interdisciplinary Research Foundation of SJTU (YG2019QNB34), and EU Horizon 2020 (Advanced Grant Scheme 740235). The authors are grateful to the Instrumental Analysis Centre of the SJTU for their assistance with material characterization and qPCR. The authors thank Prof. Rubing Liang at the School of Life Sciences of SJTU for providing facilities for cDNA synthesis and Prof. Xin Huang at the Harbin Institute of Technology for suggestions for the synthesis of the mercaptothiazoline-capped RAFT agent. Conceptualization, V.M. and H.D.; Methodology, H.D. L.L. and M.L.; Investigation, V.M. and A.Y.D.; Writing ? Original Draft, V.M.; Writing ? Review & Editing, H.D. S.M. and V.M.; Funding Acquisition, H.D.; Resources, H.D.; Visualization, P.Z.; Supervision, H.D. and S.M. The authors declare no competing interests.

Publisher Copyright:
© 2020 The Authors

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • cell/protocell cognate interaction
  • glycan-lectin interaction
  • interfacial assembly
  • polyccharidosomes
  • polysaccharide/polymer nanoconjugates
  • synergistic macrophage activation
  • synthetic virus-like particles

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