Idoia Mikelez-Alonso1, Ane Ruiz-de-Angulo1, Francisco Borrego Rabasco 2,3,*, Juan C. Mareque-Rivas1,3,*
1Theranostic Nanomedicine group, CIC biomaGUNE 2Immunopathology group, Bio Cruces Health Research Institute, 3Ikerbasque, Basque Foundation for Science 3, 48013 Bilbao, Bizkaia, Spain, *Corresponding Authors: F. Borrego, francisco.borregorabasco@osakidetza.eus; J.C. Mareque, jmareque@cicbiomagune.es
Nanoparticles (NPs) have a clinical interest because of their usefulness for non-invasive imaging, diagnosis and therapy. Using NPs in cancer immunotherapy is becoming very promising. Important challenges are targeting the therapy to specific locations1 and the induction of specific cytotoxic activity against cancer cells. Dendritic cells (DCs)2 and natural killer (NK) cells are two immune cell types currently used in cancer immunotherapy.
Harnessing these two cell types with NPs could be an effective new approach to generate robust and potent immune responses against cancer.
Several types of iron oxide NPs (IONPs) were used, with different sizes and shapes and PEG-phospholipid coatings. Mouse bone marrow derived dendritic cells (BMDCs) were generated and NK cells were obtained from human blood.
Activation and maturation of BMDCs was explored by incubating the cells with the described IONP-based systems. Migration assays were carried out incubating the cells within a transwell 24-well plate coupled to a magnetic plate. For NK cells, the proliferation rate in response to interleukin (IL)-2 was analyzed using the IONPs in a 48-well plate.
21 nm IONPs enhanced the migration of the BMDCs and induced their maturation as shown by cell surface maturation markers. They promoted the production of pro-inflammatory cytokines, such as TNF-α, IL-12 and IL-6. In addition, these 21 nm IONPs were not toxic and cooperated in the IL-2 mediated proliferation of NK cells3.
Cube shaped 21 nm IONPs coated with PEG-PLs efficiently induced activation and migration of DCs and NK cell proliferation, showing their potential to use them in cancer immunotherapy.
[1] Ruiz-de-Angulo, A.; Zabaleta, A.; Gómez-Vallejo, V.; Loop, J.; Mareque-Rivas, J.C., ACS Nano, 2016, 10, 1602-1618.
[2] Palucka, K.; Banchereau, J., Nature, 2012, 12, 265-277.
[3] F. Borrego, M.C. Alonso, M.D. Galini, J. Carracedo, R. Ramirez, B. Ostos, J. Peña, R. Solana., Experimental Gerontology 34 (1999) 253–265
Targeted drug delivery and nanocarriers , Nanomedicine for cancer diagnosis & therapy , Nano-Imaging for diagnosis, therapy and delivery
