Dual-reactive single-chain polymer nanoparticles for orthogonal functionalization through active ester and click chemistry.
J Control Release
; 373: 117-127, 2024 Sep.
Article
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymers
/
Alkynes
/
Esters
/
Nanoparticles
/
Click Chemistry
Limits:
Humans
Language:
En
Journal:
J Control Release
/
J. control. release
/
Journal of controlled release
Journal subject:
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Netherlands
Country of publication:
Netherlands