A team of scientists from the University of Granada (UGR) has carried out the synthesis, characterization, functionalization and evaluation of new nanoparticles based on nano-emulsions of olive oil. These nanocapsules carry drugs such as paclitaxel inside, which make it possible to increase the efficacy in the treatment of pancreatic cancer and avoid the adverse effects associated with this drug.
The study, which has been funded by the Ministry of Science and Innovation (MICIN), has been carried out by a team of scientists led by Juan Antonio Marchal, from the research group "Advanced Therapies: Differentiation, Regeneration and Cancer" at the University from Granada, and José Manuel Peula García from the University of Malaga, member of the Fluids and Biocolloids research group from the University of Granada; together with other researchers belonging to the Biosanitary Research Institute of Granada, the center Center Pfizer-University of Granada-Andalusian Board of Genomics and Oncology Research (GENYO) and the Unit of Excellence "Modeling Nature: from nano to macro" of the UGR .
In addition, it has also had the financial support of the Chair Drs. Galera and Requena for research on cancer stem cells. This study is part of the doctoral thesis of Saúl Abenhamar Navarro Marchal, who has been awarded the prize for the best Doctoral Thesis in the scientific-technical areas of the XIII La Rábida 2020 Ibero-American Studies Awards.
In addition to the beneficial properties of olive oil and its bioactive compounds in the prevention of cardiovascular diseases and cancer, it includes being used to transform into small smart nanovesicles that function as "Trojan horses" to carry drugs and monitor the pancreatic cancer (theranostic), as reported by the Granada center.
Thus, this research has focused on the validation of a new synthesis strategy based on natural and biocompatible products to produce functionalized olive oil nanoparticles (NPs). These NPs can carry drugs such as the one used in current chemotherapy treatments for pancreatic cancer (Paclitaxel), a dye that emits in the far infrared and, in addition, they are covered on their surface with a detector (anti-cancer antibody). CD44), which specifically binds to membrane receptors that are over-expressed on pancreatic cancer stem cells (PCMCs).
These NPs have been evaluated in vitro and in vivo using a transplantation model of human PCMCs (orthotopic xenograft) in the pancreas of mice. In vitro tests showed that NPs improve the potency of paclitaxel compared to the free drug. In vivo studies demonstrated the ability of these theranostic NPs to target exclusively the tumor area, even determining areas of distant metastasis, which indicates that this nanosystem is a good candidate for the treatment and monitoring of over-expressing tumors. CD44. Furthermore, this versatile nano-device can be easily modified to treat and control different types of cancer by adapting the conjugation strategy.
Specifically, these smart olive oil NPs have various molecules attached to their surface. Among them, the presence of poloxamer F68 stands out, which favors the stability of NPs and prevents phagocytosis by the immune system of NPs. Another molecule is epikuron, which is made up of a mixture of phospholipids. Finally, the coating of the NPs contains deoxy-cholic acid, a molecule very similar to cholesterol which allows the binding of the anti-CD44 antibody.
On the other hand, within olive oil it contains a fluorophore that emits in the far red emission spectrum, which allows monitoring of NPs both in cells and in vivo.. The chemotherapy drug used is paclitaxel and it is also dissolved in the olive oil core. This drug is currently used clinically for the treatment of pancreatic cancer, which when administered in its free form is very toxic and presents many adverse reactions such as hair loss, vomiting, sclerosis of the blood vessels, cardio-toxicity, among others and has difficulty getting in and out of PCMCs. By using it in these olive oil NPs, it has been possible to avoid all these adverse effects and to be more selective against said PCMCs. Finally, an antibody has been added that specifically recognizes a membrane receptor that is over-expressed on pancreatic cancer CMCs.
In tests carried out in cells, it has been possible to reduce the amount of paclitaxel four times to obtain a therapeutic efficacy equal to that of free paclitaxel in PCMCs, so the current dose of paclitaxel in chemotherapy treatments could be considerably reduced.
The university has underlined that the successful development of a nano-device based on biocompatible synthesis strategies for the functionalization of olive oil nanovesicles has been demonstrated for the first time. In his opinion, surprisingly, fluorescent marking allows efficient in vivo monitoring of the nano-device, being a powerful candidate for the treatment of tumors that over-express CD44, avoiding the adverse effects associated with traditional chemotherapy.
In addition, several modifications can be made to this novel nano-system that broaden the range of applications of this prototype, such as vehicleization of different drugs, the alternative use of other tracking molecules, depending on the detection technique used, and the conjugation of other specific molecules for different tumors and even for different diseases.