Matrix Metalloproteinase-Responsive Delivery of PEGylated Fibroblast Growth Factor 2.
ACS Biomater Sci Eng
; 10(1): 156-165, 2024 Jan 08.
Article
em En
| MEDLINE
| ID: mdl-37988287
ABSTRACT
Attachment of polyethylene glycol (PEG) chains is a common, well-studied, and Food and Drug Administration-approved method to address the pharmacokinetic challenges of therapeutic proteins. Occasionally, PEGylation impairs the activity of pharmacodynamics (PD). To overcome this problem, disease-relevant cleavable linkers between the polymer and the therapeutic protein can unleash full PD by de-PEGylating the protein at its target site. In this study, we engineered a matrix metalloproteinase (MMP)-responsive fibroblast growth factor 2 (FGF-2) mutant that was site-specifically extended with a PEG polymer chain. Using bioinspired strategies, the bioconjugate was designed to release the native protein at the desired structure/environment with preservation of the proliferative capacity in vitro on NIH3T3 cells. In vivo, hepatic exposure was diminished but not its renal distribution over time compared to unconjugated FGF-2. By releasing the growth factor from the PEG polymer in response to MMP cleavage, restored FGF-2 may enter hard-to-reach tissues and activate cell surface receptors or nuclear targets.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Fator 2 de Crescimento de Fibroblastos
Limite:
Animals
País como assunto:
America do norte
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article