IBS GRANADA scientists patent a new therapy, based on smart nanoparticles, to fight breast cancer
Research has shown that three times less of the clinically used drug is needed with the nanosystem designed by ibs.GRANADA researchers to produce the same therapeutic effect as current chemotherapy, clearly reducing its side effects.
The results have been patented and published in the scientific journal "Nanomedicine: Nanotechnology, Biology and Medicine"
A team of scientists from ibs.GRANADA has designed and patented a new therapy based on trifunctionalized polystyrene nanoparticles (NPs) and the bioconjugation of different molecules, including doxorubicin, to treat triple-negative breast cancer and prevent the adverse effects associated with this drug. This system has been patented and published in the prestigious scientific journal "Nanomedicine: Nanotechnology, Biology and Medicine«.
The study has been carried out by a team of scientists led by the Rosario Sanchez Martin, principal investigator of the Pharmaceutical and Organic Chemistry research group at ibs.GRANADA, of the NanoChemBio group of the Pfizer-University of Granada-Junta de Andalucía de Genomics and Oncological Research (Genyo) center and of the CTS987 group: Development of therapeutic strategies and diagnosis of the University of Granada, and John Anthony Marchal, from the research group "Advanced Therapies: Differentiation, Regeneration and Cancer" of the University of Granada, both belonging to the Biosanitary Research Institute of Granada (ibs.GRANADA) and the Units of Excellence of "Chemistry applied to Biomedicine and the Environment» and «Modeling Nature: from nano to macro» from the UGR.
The research focuses on the validation of an efficient chemical strategy for the bioconjugation of various bioactive molecules in a controlled manner in the NP and thus carry out the production of trifunctionalized polystyrene NPs. These NPs are functionalized with a drug used in current chemotherapy treatments (doxorubicin), a fluorescent marker (fluorophore) that allows monitoring of NPs, and a reference peptide (CRGDK), which allows them to specifically bind to neuropilin-1 (Nrp-1), a membrane receptor that is overexpressed in human triple negative breast cancer cells (TNBC) and not in healthy cells.
This makes it possible to direct the NPs loaded with the chemotherapeutic drug exclusively to the tumor cells, without affecting the healthy ones and, on the other hand, since the fluorophore is bound, to locate the tumor and to monitor both the efficacy of the treatment and the production of metastasis, which makes them theranostic PN (useful for both diagnosis and treatment).
Effective "in vitro» e «in vivo«
The efficacy of the effect of these NPs has been evaluated both vitro , the in vivo, using a mouse breast TNBC cell transplantation model, faithfully simulating the human breast tumor.
The essays vitro show that NPs improve the therapeutic index compared to free doxorubicin, that is, three times less amount of the drug designed in the UGR is needed to produce the same therapeutic effect than current chemotherapy, which clearly causes its side effects are minor.
The studies in vivo show that theranostic PNs are selectively directed to the tumor area, reducing its volume to the same level as the treatment with free doxorubicin. But as an advantage compared to doxorubicin in solution, these NPs do not have side effects, such as weight loss, toxicity in the nervous system or skin lesions.
This multifunctional nano-device based on bioconjugation strategies has proven to be a good candidate for the diagnosis and monitoring of tumors that overexpress Nrp-1. Furthermore, as an additional advantage it is found that this versatile nano-device can be easily adapted to treat and control other types of cancer by adapting the conjugation strategy depending on the tumor type.
The study was funded by the Ministry of Science, Innovation and Universities (MICINN) and the Carlos III Health Institute, in addition to the Office of Research Transfer (OTRI) and the "Drs. Galera and Requena Chair of Cancer Stem Cell Research" at the University of Granada.
Bibliographic reference:
A versatile theranostic nanodevice based on an orthogonal bioconjugation strategy for efficient targeted treatment and monitoring of triple negative breast cancer.
Cano-Cortes MV, Navarro-Marchal SA, Ruiz-Blas MP, Diaz-Mochon JJ, Marchal JA *, Sanchez-Martin RM *.
Nanomedicine. 2019 Oct 30; 24: 102120. doi: 10.1016 / j.nano.2019.102120.
