Rational design of diblock copolymer enables efficient cytosolic protein delivery.
J Colloid Interface Sci
; 673: 722-734, 2024 Nov.
Article
em En
| MEDLINE
| ID: mdl-38901362
ABSTRACT
Polymer-mediated cytosolic protein delivery demonstrates a promising strategy for the development of protein therapeutics. Here, we propose a new designed diblock copolymer which realizes efficient cytosolic protein delivery both in vitro and in vivo. The polymer contains one protein-binding block composed of phenylboronic acid (PBA) and N-(3-dimethylaminopropyl) (DMAP) pendant units for protein binding and endosomal escape, respectively, followed by the response to ATP enriched in the cytosol which triggers the protein release. The other block is PEG designed to improve particle size control and circulation in vivo. By optimizing the block composition, sequence and length of the copolymer, the optimal one (BP20) was identified with the binding block containing 20 units of both PBA and DMAP, randomly distributed along the chain. When mixed with proteins, the BP20 forms stable nanoparticles and mediates efficient cytosolic delivery of a wide range of proteins including enzymes, toxic proteins and CRISPR/Cas9 ribonucleoproteins (RNP), to various cell lines. The PEG block, especially when further modified with folic acid (FA), enables tumor-targeted delivery of Saporin in vivo, which significantly suppresses the tumor growth. Our results shall inspire the design of novel polymeric vehicles with robust capability for cytosolic protein delivery, which holds great potential for both biological research and therapeutic applications.
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Base de dados:
MEDLINE
Assunto principal:
Citosol
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Colloid Interface Sci
Ano de publicação:
2024
Tipo de documento:
Article