Controlled adsorption of multiple bioactive proteins enables targeted mast cell nanotherapy.
Nat Nanotechnol
; 19(5): 698-704, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38228804
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
/
Mastócitos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Nanotechnol
/
Nat. nanotechnol. (Online)
/
Nature nanotechnology (Online)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos