Abstract
Protein adsorption onto nanomaterials often results in denaturation and loss of bioactivity. Controlling the adsorption process to maintain the protein structure and function has potential for a range of applications. Here we report that self-assembled poly(propylene sulfone) (PPSU) nanoparticles support the controlled formation of multicomponent enzyme and antibody coatings and maintain their bioactivity. Simulations indicate that hydrophobic patches on protein surfaces induce a site-specific dipole relaxation of PPSU assemblies to non-covalently anchor the proteins without disrupting the protein hydrogen bonding or structure. As a proof of concept, a nanotherapy employing multiple mast-cell-targeted antibodies for preventing anaphylaxis is demonstrated in a humanized mouse model. PPSU nanoparticles displaying an optimized ratio of co-adsorbed anti-Siglec-6 and anti-FcεRIα antibodies effectively inhibit mast cell activation and degranulation, preventing anaphylaxis. Protein immobilization on PPSU surfaces provides a simple and rapid platform for the development of targeted protein nanomedicines.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 698-704 |
| Number of pages | 7 |
| Journal | Nature nanotechnology |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2024 |
Funding
This work was supported by the National Institute of Biomedical Imaging and Bioengineering (NIH grant no. 1R01EB030629-01A1) (to E.A.S.) and the National Institute of Allergy and Infectious Disease (NIH grant no. R21AI159586) (to E.A.S. and B.S.B.). We are grateful to E. W. Roth for the cryo-STEM observation. We acknowledge support from the BioCryo facility of Northwestern University\u2019s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN and Northwestern\u2019s MRSEC program (NSF DMR-1720139). SAXS analysis benefited from the use of the SasView application, originally developed under NSF award DMR-0520547. SasView contains code developed with funding from the European Union\u2019s Horizon 2020 research and innovation programme under the SINE2020 project, grant agreement no. 654000. We are also grateful for the donation of chimeric human IgE from Allakos, Inc. used in our hapten experiments.
ASJC Scopus subject areas
- Bioengineering
- Atomic and Molecular Physics, and Optics
- Biomedical Engineering
- General Materials Science
- Condensed Matter Physics
- Electrical and Electronic Engineering