Anti-tumour activity of low molecular weight heparin doxorubicin nanoparticles for histone H1 high-expressive prostate cancer PC-3M cells.
J Control Release
; 295: 102-117, 2019 02 10.
Article
en En
| MEDLINE
| ID: mdl-30582952
ABSTRACT
Nucleus-targeting drug delivery systems (NTDDs) deliver chemotherapeutic agents to nuclei in order to improve the efficacy of anti-tumour therapy. Histone H1 (H1) plays a key role in establishing and maintaining higher order chromatin structures and could bind to cell membranes. In the present study, we selected H1 as a target to prepare a novel H1-mediated NTDD. Low molecular weight heparin (LMHP) and doxorubicin (DOX) were combined to form LMHP-DOX. Then, a novel NTDD consisting of LMHP-DOX nanoparticles (LMHP-DOX NPs) was prepared by self-assembly. The characteristics of LMHP-DOX and LMHP-DOX NPs were investigated. Histone H1 high-expressive prostate cancer PC-3M cell line was selected as the cell model. Cellular uptake, and the in vitro and in vivo anti-tumour activity of LMHP-DOX NPs were evaluated on H1 high-expressive human prostate cancer PC-3M cells. Our results indicated that intact LMHP-DOX NPs mediated by H1 could be absorbed by H1 high-expressive PC-3M cells, escape from the lysosomes to the cytoplasm, and localize in the perinuclear region via H1-mediated, whereby DOX could directly enter the cell nucleus and quickly increase the concentration of DOX in the nuclei of H1 high-expressive PC-3M cells to enhance the apoptotic activity of cancer cells. The anti-coagulant activity of LMHP-DOX NPs was almost completely diminished in rat blood compared with that of LMHP, indicating the safety of LMHP-DOX NPs. Compared to traditional NTDD strategies, LMHP-DOX NPs avoid the complicated modification of nucleus-targeting ligands and provide a compelling solution for the substantially enhanced nuclear uptake of chemotherapeutic agents for the development of more intelligent NTDDs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Histonas
/
Doxorrubicina
/
Heparina de Bajo-Peso-Molecular
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China