Imidazole-Mediated Dual Location Disassembly of Acid-Degradable Intracellular Drug Delivery Block Copolymer Nanoassemblies.
Macromol Rapid Commun
; 42(16): e2100262, 2021 Aug.
Article
en En
| MEDLINE
| ID: mdl-34050688
ABSTRACT
Acid-degradable (or acid-cleavable) polymeric nanoassemblies have witnessed significant progress in anti-cancer drug delivery. However, conventional nanoassemblies designed with acid-cleavable linkages at a single location have several challenges, such as, sluggish degradation, undesired aggregation of degraded products, and difficulty in controlled and on-demand drug release. Herein, a strategy that enables the synthesis of acid-cleavable nanoassemblies labeled with acetaldehyde acetal groups in both hydrophobic cores and at core/corona interfaces, exhibiting synergistic response to acidic pH at dual locations and thus inducing rapid drug release is reported. The systematic analyses suggest that the acid-catalyzed degradation and disassembly are further enhanced by decreasing copolymer concentration (i.e., increasing proton/acetal mole ratio). Moreover, incorporation of acid-ionizable imidazole pendants in the hydrophobic cores improve the encapsulation of doxorubicin, the anticancer drug, through π-π interactions and enhance the acid-catalyzed hydrolysis of acetal linkages situated in the dual locations. Furthermore, the presence of the imidazole pendants induce the occurrence of core-crosslinking that compensates the kinetics of acetal hydrolysis and drug release. These results, combined with in vitro cell toxicity and cellular uptake, suggest the versatility of the dual location acid-degradation strategy in the design and development of effective intracellular drug delivery nanocarriers.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Micelas
Idioma:
En
Revista:
Macromol Rapid Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá