2-Hydroxyoleic Acid as a Self-Assembly Inducer for Anti-Cancer Drug-Centered Nanoparticles

• Main Authors: Antonia I. Antoniou (Author), Giulia Nordio (Author), Maria Luisa Di Paolo (Author), Eleonora Colombo (Author), Beatrice Gaffuri (Author), Laura Polito (Author), Arianna Amenta (Author), Pierfausto Seneci (Author), Lisa Dalla Via (Author), Dario Perdicchia (Author), Daniele Passarella (Author)
• Format: Book
• Published: MDPI AG, 2023-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

A potent nontoxic antitumor drug, 2-hydroxyoleic acid (<b>6</b>, 2OHOA) used for membrane lipid therapy, was selected as a self-assembly inducer due to its ability to form nanoparticles (NPs) in water. For this purpose, it was conjugated with a series of anticancer drugs through a disulfide-containing linker to enhance cell penetration and to secure drug release inside the cell. The antiproliferative evaluation of the synthesized NP formulations against three human tumor cell lines (biphasic mesothelioma MSTO-211H, colorectal adenocarcinoma HT-29, and glioblastoma LN-229) showed that nanoassemblies <b>16</b>-<b>22a,bNPs</b> exhibit antiproliferative activity at micromolar and submicromolar concentrations. Furthermore, the ability of the disulfide-containing linker to promote cellular effects was confirmed for most nanoformulations. Finally, <b>17bNP</b> induced intracellular ROS increase in glioblastoma LN-229 cells similarly to free drug <b>8</b>, and such elevated production was decreased by pretreatment with the antioxidant <i>N</i>-acetylcysteine. Also, nanoformulations <b>18bNP</b> and <b>21bNP</b> confirmed the mechanism of action of the free drugs.

Item Description

10.3390/ph16050722
1424-8247