Related Experiment Video
Updated: Aug 9, 2025
Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells
Published on: February 9, 2019
Anticancer Activity of Nano-formulated Orlistat-Dopamine Conjugates Through Self-Assembly
1Department of Chemistry and Chemical Biology, Charles V. Schaefer School of Engineering and Sciences, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States.
Abstract:
Orlistat, an FDA-approved fatty acid inhibitor for obesity treatment, demonstrates certain low and greatly varied anticancer abilities. In a previous study, we revealed a synergistic effect between orlistat and dopamine in cancer treatment. Here, orlistat-dopamine conjugates (ODCs) with defined chemical structures were synthesized. The ODC by design underwent polymerization and self-assembly in the presence of oxygen to form nano-sized particles (Nano-ODCs) spontaneously. The resulted Nano-ODCs of partial crystalline structures demonstrated good water dispersion to form stable Nano-ODC suspensions. Because of the bioadhesive property of the catechol moieties, once administered, Nano-ODCs were quickly accumulated on cell surfaces and efficiently uptaken by cancer cells. In the cytoplasm, Nano-ODC experienced biphasic dissolution followed by spontaneous hydrolysis to release intact orlistat and dopamine. Besides elevated levels of intracellular reactive oxygen species (ROS), the co-localized dopamine also induced mitochondrial dysfunctions through monoamine oxidases (MAOs)-catalyzed dopamine oxidation. The strong synergistic effects between orlistat and dopamine determined a good cytotoxicity activity and a unique cell lysis mechanism, explaining the distinguished activity of Nano-ODC to drug-sensitive and -resistant cancer cells. This new technology-enabled orlistat repurposing will contribute to overcoming drug resistance and the improvement of cancer chemotherapy.
Insights
This study synthesized novel nano-sized orlistat-dopamine conjugates (Nano-ODCs) that exhibit potent synergistic anticancer effects. Nano-ODCs effectively target cancer cells, overcoming drug resistance and enhancing chemotherapy outcomes.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Orlistat, an FDA-approved obesity drug, has shown limited anticancer properties.
- A previous study identified a synergistic effect between orlistat and dopamine in cancer treatment.
- Drug resistance remains a significant challenge in cancer chemotherapy.
Purpose of the Study:
- To synthesize and characterize orlistat-dopamine conjugates (ODCs) for cancer therapy.
- To investigate the self-assembly and properties of Nano-ODCs.
- To evaluate the anticancer efficacy and mechanism of Nano-ODCs against drug-sensitive and -resistant cancer cells.
Main Methods:
- Synthesis of orlistat-dopamine conjugates (ODCs).
- Spontaneous polymerization and self-assembly of ODCs into nano-sized particles (Nano-ODCs) in the presence of oxygen.
- Characterization of Nano-ODCs' structure, dispersion, and bioadhesive properties.
- In vitro evaluation of Nano-ODCs' cellular uptake, dissolution, dopamine release, and cytotoxicity.
- Assessment of intracellular reactive oxygen species (ROS) levels and mitochondrial dysfunction induced by Nano-ODCs.
Main Results:
- Nano-ODCs were successfully synthesized, exhibiting partial crystalline structures and forming stable suspensions.
- Nano-ODCs demonstrated efficient cellular accumulation and uptake due to bioadhesive catechol moieties.
- Intracellular release of orlistat and dopamine led to elevated ROS and dopamine-induced mitochondrial dysfunction via MAO catalysis.
- Significant synergistic cytotoxicity was observed, with Nano-ODCs effectively targeting both drug-sensitive and -resistant cancer cells.
- A unique cell lysis mechanism was identified, contributing to the observed anticancer activity.
Conclusions:
- Orlistat repurposing through conjugation with dopamine and nano-assembly offers a promising strategy for cancer chemotherapy.
- Nano-ODCs exhibit potent synergistic anticancer activity by inducing ROS and mitochondrial dysfunction.
- This novel approach demonstrates potential in overcoming drug resistance and improving cancer treatment outcomes.
