LEPABE (UPorto) researchers developed a nanosystem for Glioblastoma multiform therapy

Researchers from LEPABE have successfully developed a nanovehicle for the treatment of Glioblastoma Multiforme. This study was published in the "International Journal of Pharmaceutics”.  The development of this nanosystem intended to increase the therapeutic efficacy of temozolomide. Glioblastoma multiform is the most common and invasive type of malignant brain tumour. This neoplasia presents high morbidity and mortality with an average survival rate of up to one year. Although temozolomide is the first-line treatment of this type of tumour, its administration exhibits several problems, such as low bioavailability and harmful effects to the healthy tissues. The group proposed the use of poly (lactic-co-glycolic acid) nanoparticles for the encapsulation and delivery of the drug. To increase the specificity of the developed nanosystem, the group modified the surface of the nanoparticles with antibodies against the transferrin-receptor. Transferrin is an essential protein involved in the iron’s metabolism maintenance. This molecule overexpressed in the blood-brain barrier and in tumour cells. Thus, suing these antibody moieties, ensures that the nanovehicle is able to cross this biological barrier, reaching the target cells at effective therapeutic doses, increasing drug’s efficacy and decreasing its toxicity in healthy tissues. The developed nanosystem showed to be extremely effective in improving the antitumor activity of this drug, showing clear efficacy in the therapeutic effects.

Authors and affiliations:

Maria João Ramalho¹, Emmanuel Sevin², Fabien Gosselet², Jorge Lima³, Manuel Álvaro Neto Coelho¹, Joana Angélica Loureiro¹ e Maria do Carmo Pereira¹

¹. LEPABE – Laboratory for Process Engineering, Environment, Biotechnology and Energy, Porto, Portugal

². Blood-brain Barrier LABORATORY (LBHE), University of Artois, Lens, France

Faculty of Medicine, University of Porto, Porto, Portugal

³. i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal

Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

Abstract:
Glioblastoma multiforme is the most lethal type of brain tumour and the established therapy only extends patients survival to approximately one year. Its first-line treatment is based on of chemotherapy with the alkylating agent temozolomide (TMZ). As many other chemotherapeutic drugs, TMZ presents several limitations as high toxicity and low bioavailability. The delivery of TMZ using poly (lactic-co-glycolic acid) nanoparticles is proposed in this work. Stable nanoparticles functionalized with an OX26 type monoclonal antibody for transferrin receptor were developed, targeting the glioblastoma tumour cells, since these cells are known for overexpressing this receptor. The release profile of TMZ from the nanoparticles was studied mimicking physiological conditions, and targeted cellular internalization was also investigated. Two glioblastoma cell lines – U215 and U87 – were used to evaluate the in vitro cytotoxicity of the drug, showing that the prepared nanocarriers enhance the anticancer activity of TMZ. The functionalization with the monoclonal antibody for transferrin receptor proved to be advantageous in enhancing the cellular internalization in glioblastoma cells.

Journal: International Journal of Pharmaceutics

Link: https://doi.org/10.1016/j.ijpharm.2018.04.062