Programmable Peptides Activated Macropinocytosis for Direct Cytosolic Delivery.
Adv Healthc Mater
; 12(27): e2301162, 2023 10.
Article
en En
| MEDLINE
| ID: mdl-37449948
ABSTRACT
Bioactive macromolecules show great promise for the treatment of various diseases. However, the cytosolic delivery of peptide-based drugs remains a challenging task owing to the existence of multiple intracellular barriers and ineffective endosomal escape. To address these issues, herein, programmable self-assembling peptide vectors are reported to amplify cargo internalization into the cytoplasm through receptor-activated macropinocytosis. Programmable self-assembling peptide vector-active human epidermal growth factor receptor-2 (HER2) signaling induces the receptor-activated macropinocytosis pathway, achieving efficient uptake in tumor cells. Shrinking macropinosomes accelerate the process of assembly dynamics and form nanostructures in the cytoplasm to increase peptide-based cargo accumulation and retention. Inductively coupled plasma mass (ICP-MS) spectrometry quantitative analysis indicates that the Gd delivery efficiency in tumor tissue through the macropinocytosis pathway is improved 2.5-fold compared with that through the use of active targeting molecular delivery. Finally, compared with nanoparticles and active targeting delivery, the delivery of bioactive peptide drugs through the self-assembly of peptide vectors maintains high drug activity (the IC50 decreased twofold) in the cytoplasm and achieves effective inhibition of tumor cell growth. Programmable self-assembling peptide vectors represent a promising platform for the intracellular delivery of diverse bioactive drugs, including molecular drugs, peptides, and biologics.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Nanoestructuras
Idioma:
En
Revista:
Adv Healthc Mater
Año:
2023
Tipo del documento:
Article