Modifying the Backbone Chemistry of PEG-Based Bottlebrush Block Copolymers for the Formation of Long-Circulating Nanoparticles.
Adv Healthc Mater
; 13(22): e2304040, 2024 Sep.
Article
de En
| MEDLINE
| ID: mdl-38734871
ABSTRACT
Nanoparticle physicochemical properties have received great attention in optimizing the performance of nanoparticles for biomedical applications. For example, surface functionalization with small molecules or linear hydrophilic polymers is commonly used to tune the interaction of nanoparticles with proteins and cells. However, it is challenging to control the location of functional groups within the shell for conventional nanoparticles. Nanoparticle surfaces composed of shape-persistent bottlebrush polymers allow hierarchical control over the nanoparticle shell but the effect of the bottlebrush backbone on biological interactions is still unknown. The synthesis is reported of novel heterobifunctional poly(ethylene glycol) (PEG)-norbornene macromonomers modified with various small molecules to form bottlebrush polymers with different backbone chemistries. It is demonstrated that micellar nanoparticles composed of poly(lactic acid) (PLA)-PEG bottlebrush block copolymer (BBCP) with neutral and cationic backbone modifications exhibit significantly reduced cellular uptake compared to conventional unmodified BBCPs. Furthermore, the nanoparticles display long blood circulation half-lives of ≈22 hours and enhanced tumor accumulation in mice. Overall, this work sheds light on the importance of the bottlebrush polymer backbone and provides a strategy to improve the performance of nanoparticles in biomedical applications.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Polyéthylène glycols
/
Nanoparticules
Limites:
Animals
/
Humans
Langue:
En
Journal:
Adv Healthc Mater
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique
Pays de publication:
Allemagne