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

• 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: English
• 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
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S331578

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.