Cascade-targeting polymeric particles eliminate intracellular C. neoformans in fungal infection therapy.
J Control Release
; 373: 399-409, 2024 Jul 24.
Article
en En
| MEDLINE
| ID: mdl-39033984
ABSTRACT
C. neoformans, a life-threatening invasive fungal pathogen, can hijack the pulmonary macrophages as 'Trojan horse', leading to cryptococcal meningitis and recurrence. Combatting these elusive fungi has posed a long-standing challenge. Here, we report an inhaled cascade-targeting drug delivery platform that can sequentially target host cells and intracellular fungi. The delivery system involves encapsulating amphotericin B (AMB) into polymeric particles decorated with AMB, creating a unique surface pattern, denoted as APP@AMB. The surface topology of APP@AMB guides the efficient macrophages internalization and intracellular drugs accumulation. Following endocytosis, the surface-functionalized AMB specifically targets intracellular fungi by binding to ergosterol in the fungal membrane, as demonstrated through co-localization studies using confocal microscopy. Through on-site AMB delivery, APP@AMB displays superior efficacy in eliminating C. neoformans in the lungs and brain compared to free AMB following inhalation in infected mice. Additionally, APP@AMB significantly alleviates the nephrotoxicity associated with free AMB inhalation therapy. Thus, this biocompatible delivery system enabling host cells and intracellular fungi targeting in a cascade manner, provides a new avenue for the therapy of fungal infection.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS