Skip to main content
Log in

Preparation and characterization of enzyme-responsive zwitterionic nanoparticles for monoclonal antibody delivery

  • Research Article
  • Published:
Frontiers of Materials Science Aims and scope Submit manuscript

Abstract

Monoclonal antibodies have been used in many diseases, but how to improve their delivery efficiency is still a key issue. As the modification of zwitterionic polymers can maintain the stability and biological activity of monoclonal antibodies, in this study, zwitterionic monomers, sulfobetaine methacrylate (SBMA), and 3-[[2-(methacryloyloxy) ethyl] dimethylammonio] propionate (CBMA) were used to prepare monoclonal antibody-loaded zwitterionic nanoparticles with the aid of the crosslinker of MMP-2 enzyme-responsive peptide which was a rapid synthesis process under mild conditions. The results from dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) indicated that a series of zwitterionic nanoparticles had been successfully prepared by the in situ free radical polymerization using the MMP-2 enzyme-responsive peptide as the cross-linking agent. These nanoparticles were spherical with the sizes of (18.7±1.9) nm (SBMA nanoparticle) and (18.2±2.1) nm (CBMA nanoparticle), and the surface contained zwitterionic polymers. It was revealed that they had no cytotoxicity, could be released in tumor microenvironment by enzyme to inhibit the growth of tumor cells, and was able to effectively penetrate endothelial cells (> 2%) by transwell. Therefore, the development of this strategy has a great prospect for the delivery of monoclonal antibodies.

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. Pandit R, Chen L, Götz J. The blood–brain barrier: physiology and strategies for drug delivery. Advanced Drug Delivery Reviews, 2020, 165–166: 1–14

    Article  Google Scholar 

  2. Lin M, You R, Liu Y P, et al. Beneficial effects of anti-EGFR agents, Cetuximab or Nimotuzumab, in combination with concurrent chemoradiotherapy in advanced nasopharyngeal carcinoma. Oral Oncology, 2018, 80: 1–8

    Article  CAS  Google Scholar 

  3. McDaid W J, Greene M K, Johnston M C, et al. Repurposing of Cetuximab in antibody-directed chemotherapy-loaded nanoparticles in EGFR therapy-resistant pancreatic tumours. Nanoscale, 2019, 11(42): 20261–20273

    Article  CAS  Google Scholar 

  4. Abbott N J, Rönnbäck L, Hansson E. Astrocyte–endothelial interactions at the blood–brain barrier. Nature Reviews Neuroscience, 2006, 7(1): 41–53

    Article  CAS  Google Scholar 

  5. Abbott N J, Romero I A. Transporting therapeutics across the blood–brain barrier. Molecular Medicine Today, 1996, 2(3): 106–113

    Article  CAS  Google Scholar 

  6. Vermonden T, Censi R, Hennink W E. Hydrogels for protein delivery. Chemical Reviews, 2012, 112(5): 2853–2888

    Article  CAS  Google Scholar 

  7. Gu Z, Biswas A, Zhao M, et al. Tailoring nanocarriers for intracellular protein delivery. Chemical Society Reviews, 2011, 40(7): 3638–3655

    Article  CAS  Google Scholar 

  8. Cui Y, Cui P, Chen B, et al. Monoclonal antibody: formulations of marketed products and recent advances in novel delivery system. Drug Development and Industrial Pharmacy, 2017, 43(4): 519–530

    Article  CAS  Google Scholar 

  9. Rizvi S A A, Saleh A M. Applications of nanoparticle systems in drug delivery technology. Saudi Pharmaceutical Journal, 2018, 26(1): 64–70

    Article  Google Scholar 

  10. Duncan R, Gaspar R. Nanomedicine(s) under the microscope. Molecular Pharmaceutics, 2011, 8(6): 2101–2141

    Article  CAS  Google Scholar 

  11. Kumar Khanna V. Targeted delivery of nanomedicines. International Scholarly Research Notices, 2012, 2012

  12. Zhao Z, Nelson A R, Betsholtz C, et al. Establishment and dysfunction of the blood-brain barrier. Cell, 2015, 163(5): 1064–1078

    Article  CAS  Google Scholar 

  13. Li J, Guo Y, Kuang Y, et al. Choline transporter-targeting and co-delivery system for glioma therapy. Biomaterials, 2013, 34(36): 9142–9148

    Article  CAS  Google Scholar 

  14. Tian H, Du J, Wen J, et al. Growth-factor nanocapsules that enable tunable controlled release for bone regeneration. ACS Nano, 2016, 10(8): 7362–7369

    Article  CAS  Google Scholar 

  15. Li S, Chen L, Huang K, et al. Tumor microenvironment-tailored weakly cell-interacted extracellular delivery platform enables precise antibody release and function. Advanced Functional Materials, 2019, 29(43): 1903296

    Article  CAS  Google Scholar 

  16. Mikitsh J L, Chacko A M. Pathways for small molecule delivery to the central nervous system across the blood–brain barrier. Perspectives in Medicinal Chemistry, 2014, 6: doi:https://doi.org/10.4137/PMC.S13384

  17. Leeson P D, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nature Reviews. Drug Discovery, 2007, 6(11): 881–890

    Article  CAS  Google Scholar 

  18. He Q, Liu J, Liang J, et al. Towards improvements for penetrating the blood–brain barrier — recent progress from a material and pharmaceutical perspective. Cells, 2018, 7(4): 24

    Article  Google Scholar 

  19. Jones A R, Shusta E V. Blood–brain barrier transport of therapeutics via receptor-mediation. Pharmaceutical Research, 2007, 24(9): 1759–1771

    Article  CAS  Google Scholar 

  20. Chen Y, Dalwadi G, Benson H A E. Drug delivery across the blood–brain barrier. Current Drug Delivery, 2004, 1(4): 361–376

    Article  CAS  Google Scholar 

  21. Alves C G, de Melo-Diogo D, Lima-Sousa R, et al. IR780 loaded sulfobetaine methacrylate-functionalized albumin nanoparticles aimed for enhanced breast cancer phototherapy. International Journal of Pharmaceutics, 2020, 582: 119346

    Article  CAS  Google Scholar 

  22. Men Y, Peng S, Yang P, et al. Biodegradable zwitterionic nanogels with long circulation for antitumor drug delivery. ACS Applied Materials & Interfaces, 2018, 10(28): 23509–23521

    Article  CAS  Google Scholar 

  23. Wang Y, He L, Yu B, et al. ZnO quantum dots modified by pH-activated charge-reversal polymer for tumor targeted drug delivery. Polymers, 2018, 10(11): 1272

    Article  Google Scholar 

  24. Han X, Li S, Li X, et al. The effect of zwitterionic surface content on blood circulation time of nanocapsule. Journal of Biomaterials Applications, 2020, 35(3): 371–384

    Article  CAS  Google Scholar 

  25. Han L, Liu C, Qi H, et al. Systemic delivery of monoclonal antibody to the central nervous system for brain tumor therapy. Advanced Materials, 2019, 31(19): 1805697

    Article  Google Scholar 

  26. Anderson N M, Simon M C. The tumor microenvironment. Current Biology, 2020, 30(16): R921–R925

    Article  CAS  Google Scholar 

  27. Cabral-Pacheco G A, Garza-Veloz I, Castruita-De la Rosa C, et al. The roles of matrix metalloproteinases and their inhibitors in human diseases. International Journal of Molecular Sciences, 2020, 21(24): 9739

    Article  CAS  Google Scholar 

  28. Chen N, Li S, Li X, et al. Construction of enzymatic nanoreactors with high catalytic activity in millifluidic systems for cancer therapy. Chemical Engineering Journal, 2022, 429: 132305

    Article  CAS  Google Scholar 

  29. Li X, Li S, Qi H, et al. Early healing of alveolar bone promoted by microRNA-21-loaded nanoparticles combined with Bio-Oss particles. Chemical Engineering Journal, 2020, 401: 126026

    Article  CAS  Google Scholar 

  30. Liang S, Liu Y, Jin X, et al. Phosphorylcholine polymer nanocapsules prolong the circulation time and reduce the immunogenicity of therapeutic proteins. Nano Research, 2016, 9(4): 1022–1031

    Article  CAS  Google Scholar 

  31. Qi H, Yang L, Li X, et al. Systemic administration of enzyme-responsive growth factor nanocapsules for promoting bone repair. Biomaterials Science, 2019, 7(4): 1675–1685

    Article  CAS  Google Scholar 

  32. Liu C, Wen J, Meng Y, et al. Efficient delivery of therapeutic miRNA nanocapsules for tumor suppression. Advanced Materials, 2015, 27(2): 292–297

    Article  Google Scholar 

  33. Del Vecchio C A, Giacomini C P, Vogel H, et al. EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms. Oncogene, 2013, 32(21): 2670–2681

    Article  CAS  Google Scholar 

  34. Mazorra Z, Chao L, Lavastida A, et al. Nimotuzumab: beyond the EGFR signaling cascade inhibition. Seminars in Oncology, 2018, 45(1–2): 18–26

    Article  CAS  Google Scholar 

  35. Wen J, Wu D, Qin M, et al. Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice. Nature Biomedical Engineering, 2019, 3(9): 706–716

    Article  CAS  Google Scholar 

  36. Xu D, Wu D, Qin M, et al. Efficient delivery of nerve growth factors to the central nervous system for neural regeneration. Advanced Materials, 2019, 31(33): 1900727

    Article  Google Scholar 

  37. Meng X, Zhao Y, Han B, et al. Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways. Nature Communications, 2020, 11(1): 594

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 51773151) and the Tianjin Applied Basic Research Multi-Input Fund (21JCYBJC01560). Thank Miss Yiou Lyu for her help in article writing and editing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xubo Yuan.

Ethics declarations

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hou, C., Xing, H. & Yuan, X. Preparation and characterization of enzyme-responsive zwitterionic nanoparticles for monoclonal antibody delivery. Front. Mater. Sci. 17, 230667 (2023). https://doi.org/10.1007/s11706-023-0667-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11706-023-0667-3

Keywords

Navigation