Bottlebrush Polymer-Conjugated Melittin Exhibits Enhanced Antitumor Activity and Better Safety Profile.
ACS Appl Mater Interfaces
; 13(36): 42533-42542, 2021 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-34472829
ABSTRACT
Despite potency against a variety of cancers in preclinical systems, melittin (MEL), a major peptide in bee venom, exhibits non-specific toxicity, severe hemolytic activity, and poor pharmacological properties. Therefore, its advancement in the clinical translation system has been limited to early-stage trials. Herein, we report a biohybrid involving a bottlebrush-architectured poly(ethylene glycol) (PEG) and MEL. Termed pacMEL, the conjugate consists of a high-density PEG arrangement, which provides MEL with steric inhibition against protein access, while the high molecular weight of pacMEL substantially enhances plasma pharmacokinetics with a â¼10-fold increase in the area under the curve (AUC∞) compared to free MEL. pacMEL also significantly reduces hepatic damage and unwanted innate immune response and all but eliminated hemolytic activities of MEL. Importantly, pacMEL passively accumulates at subcutaneously inoculated tumor sites and exhibits stronger tumor-suppressive activity than molecular MEL. Collectively, pacMEL makes MEL a safer and more appealing drug candidate.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
/
Meliteno
/
Neoplasias
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Asunto de la revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos