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Aragonese scientists introduce hollow gold nanoparticles into tiny vesicles (exosomes), like a Trojan horse, which when reaching tumor areas are heated with a laser, producing cell death and a strong reduction of tumors, even in metastasis processes
The prestigious journal Journal of Extracellular Vesicles, the one with the highest impact index in the field of exosomes, publishes this work, led by Pilar Martín-Duque and Jesús Santamaría, teaching and research staff at the University of Zaragoza
Aragonese scientists have developed smart shuttles to transport nanoparticles to inside by tumor cells y destroy them through heat and without drugs, following the digital workplace strategy "Troy Horse", as published today prestigious magazine Journal of Extracellular Vesicles, the one with the highest impact index in the field of exosomes.
The article collects the work led by Pilar Martín-Duque and Jesús Santamaría, teaching and research staff of the University of Zaragoza and both members of the Aragón Health Research Institute (IIS Aragon) and the Biomedical Research Network Center for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Santamaría also belongs to the Institute of Nanoscience and Materials of Aragón (INMA, mixed center CSIC-UNIZAR).
In the study "Transfer of photothermal nanoparticles using stem cell derived small extracellular vesicles for in vivo treatment of primary and multinodular tumors” also participate researchers from the University of ZaragozaMaríaSancho, Víctor Sebastián y Miguel Encinas, also attached to INMA and CIBER-BBN, along with Lluis Luján and Estela Pérez, linked to the Agri-Food Institute of Aragon, (IA2, mixed center UNIZE-QUOTE).
The authors have used cell vesicles (exosomes) as trojan horses to go hollow gold nanoparticles to the interior of tumors in animal models. “We have achieved reduce or eliminate tumors in mice without drugs, only with the heat generated when irradiated with a laser. That is, we inject the exosomes with the nanoparticles into the mouse's tail and they alone "search" for the tumor", not only in conventional models but also in multinodular ones, similar to metastasis processes," point out the authors of the work..
The results obtained with this work represent a second very important advance in the research trajectory that they have been developing for some time. Thus, in 2019, these scientists already used exosomes like trojan horses to carry catalysts Palladium (Pd) to the inside of cancer cells and manufacture the chemotherapy drug “in situ”, but the demonstration was done only with cells. In this work a further step is taken, in models in vivo.
Nanotechnology in Oncology
One of the most interesting aspects of nanotechnology are nanoparticles for oncology treatments. There are All types: toxic in themselves, capable of hosting compounds chemotherapy, capable of become hot or emit electromagnetic radiation…However, all of these structures ran into the same problem: It was very difficult to selectively reach the tumor and produce cell death only inside it..
Hitherto the main strategies to carry the particles to the tumors were two types, based on the EPR effect (which takes advantage of defects in tumor vascularization to introduce nanoparticles) and active routing calls, that decorate the particles with a wide variety of biomolecules, especially antibodies, as tumor recognition agents. Despite these efforts, recent studies have shown that only a small fraction of the nanoparticles (generally less than 1%) reached the tumors.
A study that improves access to tumors
The work presented today makes an important difference in this aspect: the authors have used cellular vesicles (exosomes) as trojan horses to carry gold nanoparticles into tumors in animal models. “We have used the natural biogenesis process of exosomes to obtain vesicles loaded with gold nanoparticles, and These vesicles have demonstrated their ability to strongly improve access to tumors regarding the EPR effect, and not only in a “xenograft” model, but in a multinodular model, which simulates metastatic growth invading the spleen and pancreas", says the professor of the Faculty of Medicine, Pilar Martín-Duque.
“I am convinced that extracellular vesicles and, particularly exosomes, have the key to leaving behind some limitations of Nanomedicine"Says Jesus Santamaría, Professor of Chemical Engineering at the University of Zaragoza, which has two Advanced Grants from the ERC. And he adds: “Although there is still a long way to go to achieve truly selective delivery, active addressing combination that exosomes provide and Remote activation of hyperthermia particles “It opens up extraordinary possibilities.”
A treatment without drugs but that uses heat
This work has used hollow gold nanoparticles, already developed by the group in previous research, which belong to what is known as “plasmonic nanoparticles” and which have the ability to heat up when receiving near-infrared radiation, the one with the greatest penetration into the body. It is, therefore, a drug-free treatment, which uses the heat generated by the particles to produce cell death around them. But "These particles are of no use if you cannot get them to the tumor., and this is where exosomes are involved, the fundamental piece in this strategy of Trojan Horse”, Highlights Pilar Martín-Duque.
The system is in principle very safe because the hyperthermia particles are only activated when illuminated by the laser (that is, even if there are particles in healthy tissues outside the tumor, only those in the laser beam would be activated). However, it is critical to obtain a sufficient mass of nanoparticles to have the desired effect. That is why it is necessary to increase the number of particles that reach the tumor. According to Santa Maria, “delivery via exosomes still needs to be perfected, but despite everything In this work we have shown that double (and in some cases triple) particles reach the tumor than when the same amount is delivered using the EPR effect.".
“Smart” Vectors
This work can be considered as a first step towards the ideal therapeutic vector: on the one hand, the selective tropism of exosomes, who are capable of recognize other cell membranes (such as those of cells of the same lineage, or tumor cells, in the case of mesenchymal stem cell exosomes). On the other hand, one highly biocompatible cargo (hollow gold particles) which, however, become lethal when illuminated with light of the appropriate wavelength. In the authors' laboratory, the use of c strategies is investigated.trojan horse to deliver therapeutic particles to the tumor (metallic particles capable of heating the environment through hyperthermia, or catalysts that generate toxic molecules once they reach the tumor).
Bibliographic reference:Transfer of photothermal nanoparticles using stem cell derived small extracellular vesicles for in vivo treatment of primary and multinodular tumors María Sancho-Albero, Miguel Encinas-Giménez, Víctor Sebastián, Estela Pérez, Lluis Luján, Jesús Santamaría, Pilar Martín-Duque Journal of Extracellular Vesicles 2022
