Antitumor Activity of α-Linolenic Acid-Paclitaxel Conjugate Nanoparticles: In vitro and in vivo

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 (A...

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Bibliographic Details
Published in:	International journal of nanomedicine 2021-01, Vol.16, p.7269-7281
Main Authors:	Xu, Mei-Qi, Hao, Yan-Li, Wang, Jing-Ru, Li, Zhuo-Yue, Li, Hui, Feng, Zhen-Han, Wang, Hui, Wang, Jing-Wen, Zhang, Xuan
Format:	Article
Language:	eng
Subjects:	alpha-Linolenic Acid Animals Antineoplastic Agents - pharmacology Antineoplastic Agents, Phytogenic antitumor activity Blood-brain barrier Brain cancer Brain research Breast cancer Cancer therapies Cell culture Cell Line, Tumor cellular uptake Chemotherapy Chromatography Drugs Endocytosis Mass spectrometry Mice Nanoparticles NMR Nuclear magnetic resonance Original Research Paclitaxel Particle size Polyethylene glycol Proteins Scientific imaging Signal transduction α-linolenic acid α-linolenic acid-paclitaxel conjugate α-linolenic acid-paclitaxel conjugate nanoparticles
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Summary:	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. 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. 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. 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.
ISSN:	1178-2013 1176-9114 1178-2013