Investigation Group. (Photo: CIBER)
Researchers from the CIBER of Bioengineering, Biomaterials and Nanomedicine, from the Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau and from the Autonomous University of Barcelona (UAB) (Catalunya, Spain) have developed a new pharmaceutical form of subcutaneous administration and release of targeted nanoparticles that selectively removes metastatic stem cells, inducing a powerful metastasis prevention effect.
The team of researchers of the CIBER-BBN, formed by the group of Antonio Villaverde and Esther Vázquez, of the Institute of Biotechnology and Biomedicine of the UAB (IBB) and led by Ramón Mangues, of the Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – IIB Sant Pau, has created inclusion bodies that, when administered subcutaneously in mice, release soluble cytotoxic nanoparticles continuously. These nanoparticles are carriers of Pseudomonas aeruginosa, which manages to maintain a stable concentration of this nanomedicine in the blood and tissues.
The results have been published in Advanced Materials, one of the most prestigious international scientific journals in Nanomedicine and Materials Science.
Dr. Mangues explains that “this new pharmaceutical form of subcutaneous administration for sustained release allows high doses of this nanopharmaceutical to be administered, at prolonged intervals (weeks in mice and probably months in humans) without toxicity at the injection site or in normal tissues, while generating a powerful antimetastatic effect”. “The development of the drug for administration in humans would reduce the need to inject frequent doses, intravenously, of current cytotoxic antitumor drugs, which requires hospitalization,” adds IIB researcher Sant Pau.
Apart from being controlled-release systems, these nanoparticles incorporate a ligand that interacts with the receptor (CXCR4), present at high levels in the membrane of metastatic stem cells capable of generating metastases (CMM CXCR4 +). Once the new pharmaceutical form is administered subcutaneously in mice with metastatic colorectal cancer, this ligand directs each nanoparticle released by this structure to the tumor tissues, increasing their uptake, to specifically internalize in the CXCR4 + CMMs and induce their selective destruction.
“This effect achieves a notable reduction in tumor size in the colon while blocking the development of lymph node, lung, liver and peritoneal metastases, without appreciable uptake or toxicity in non-tumor tissues,” the researchers explain, who have been working closely together for more than a decade.
The researchers estimate that this new therapeutic strategy will have a high clinical impact by reducing the requirement of its hospital administration, which most antitumor drugs have, and blocking metastatic dissemination, responding to an unmet clinical need. On the other hand, this new pharmaceutical form, which combines sustained release with targeting to the CXCR4 receptor, could be used in the treatment of at least 23 types of cancer that also express high levels of this receptor in tumor cells.
The new therapy offers an answer to the urgent medical need to inhibit the development of metastases, which represents the leading cause of death in cancer patients. The selective destruction of tumor and metastatic cells increases the therapeutic index of nanomedicine, obtaining a potent antimetastatic effect without generating associated adverse effects, which differentiates it from most of the currently used antitumor drugs.
Source: CIBER / DICYT and Amazings® / NCYT® | (Noticiasdelaciencia.com / Amazings.com).https://noticiasdelaciencia.com/art/36651/un-new-farmaco-inteligente-acaba-con-las-celulas-de-la-metastasis-de-manera-selectiva