Antitumor Activity of α-Linolenic Acid-Paclitaxel Conjugate Nanoparticles: In vitro and in vivo.
Int J Nanomedicine
; 16: 7269-7281, 2021.
Article
in En
| MEDLINE
| ID: mdl-34737564
ABSTRACT
PURPOSE:
Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo.METHODS:
We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated.RESULTS:
The size of ALA-PTX NPs was approximately 110.7±1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5-2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models.CONCLUSION:
ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nanoparticles
/
Antineoplastic Agents
/
Antineoplastic Agents, Phytogenic
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Nanomedicine
Year:
2021
Document type:
Article