Dual-reactive single-chain polymer nanoparticles for orthogonal functionalization through active ester and click chemistry.
J Control Release
; 373: 117-127, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38968970
ABSTRACT
Glucose has been extensively studied as a targeting ligand on nanoparticles for biomedical nanoparticles. A promising nanocarrier platform are single-chain polymer nanoparticles (SCNPs). SCNPs are well-defined 5-20 nm semi-flexible nano-objects, formed by intramolecularly crosslinked linear polymers. Functionality can be incorporated by introducing labile pentafluorophenyl (PFP) esters in the polymer backbone, which can be readily substituted by functional amine-ligands. However, not all ligands are compatible with PFP-chemistry, requiring different ligation strategies for increasing versatility of surface functionalization. Here, we combine active PFP-ester chemistry with copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry to yield dual-reactive SCNPs. First, the SCNPs are functionalized with increasing amounts of 1-amino-3-butyne groups through PFP-chemistry, leading to a range of butyne-SCNPs with increasing terminal alkyne-density. Subsequently, 3-azido-propylglucose is conjugated through the glucose C1- or C6-position by CuAAC click chemistry, yielding two sets of glyco-SCNPs. Cellular uptake is evaluated in HeLa cancer cells, revealing increased uptake upon higher glucose-surface density, with no apparent positional dependance. The general conjugation strategy proposed here can be readily extended to incorporate a wide variety of functional molecules to create vast libraries of multifunctional SCNPs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Alquinos
/
Ésteres
/
Nanopartículas
/
Química Clic
Límite:
Humans
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Países Bajos