Flavia Fontana
University of Helsinki
Flavia Fontana received her MSc in Pharmacy (2014) from the University of Pavia, Italy. She is currently a second year graduate student at the Faculty of Pharmacy, University of Helsinki, in Dr. Santos' research group. Her thesis work focuses on the development of innovative nanovectors as vaccines for cancer immunotherapy by microfluidics.
Introduction
Cancer is a very challenging disease and new approaches are sought to help in its treatment. Cancer immunotherapy involves the patient’s own immune system in the fight against the tumors using antibodies directed to the so-called “check-point inhibitors” or by the administration of chimeric T-lymphocytes. It is envisaged that the administration of nanoparticles in cancer vaccines would lead to a decrease in the side effects of the drugs, helping targeted drug delivery, and increasing the efficacy of the therapy due to the adjuvant properties of the particles themselves [1].
Porous silicon (PSi) is a biocompatible porous material which presents adjuvant-like properties [2]. Acetylated dextran (AcDX) and spermine-modified AcDX (SpAcDX) are chemically-modified polymers derived from dextran, a FDA approved material, able to stimulate an immune response by the activation of Toll-like receptors [3].
Methods
Multistage nanovectors were prepared by nanoprecipitation during glass capillary microfluidics [4]. PSi nanoparticles were encapsulated in a polymeric matrix made of AcDEX. The immunostimulant properties of the nanoparticles were assessed in vitro on human immortalized immune cells and blood-derived monocytes.
Results
The developed nanosystems induced the expression of co-stimulatory factors (CD86) in, for example, peripheral blood monocytes (Fig.1).
Discussion
The multistage nanovectors, produced with different polymers promoted the expression of CD86 from human monocytes, KG 1, and BDCM (results not shown). Moreover, the system modified with membranes derived from cancer cells showed the highest levels of CDs stimulation, with a statistically significant difference compared to the particles with the polymer alone.
Conclusions
The developed systems promoted the expression of costimulatory factors (CD86) confirming their adjuvant properties that make them suitable platforms for further development as cancer vaccines.
References
[1] D.J. Irvine,M.C. Hanson, 115 Chem Rev (2015), 11109-46.
[2] M.A. Shahbazi,T.D. Fernandez, Biomaterials 35 (2014), 9224-35.
[3] L. Cui,J.A. Cohen, Bioconjug Chem 22 (2011), 949-57.
[4] D. Liu,S. Cito, Adv Mater 27 (2015), 2298-304.
Acknowledgements
Financial support from the Academy of Finland (Grants No. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council (FP/2007-2013, Grant 310892) is greatly acknowledged.
Nanomedecine for cancer diagnosis & therapy , Microfluidics in nanomedicine and nanobiology
