Interaction of nanoparticles-tumor specific monoclonal antibodies complex with polymorphonuclear cells

MITAROTONDA ROMINA; GIORGI EXEQUIEL; CERNY NATACHA; FERNANDEZ MARISA; DESIMONE MARTIN; DE MARZI MAURICIO

Congreso; VII reunión anual Internacional de la sociedad argentina de nanomedicina; 2016

Cancer can be treated by surgery, chemotherapy, radiationtherapy, hormonal therapy, and target therapy. Ho􀁙ever, thesetreatments often have severe side effects that limit their efficacy.To improve therapy efficiency, tumor specific monoclonal antibodies􀀊mAb􀀋 are currently used. For instance, anti􀀏HE􀀴􀀏􀀔 mAbTrastuzumab (TZ) used to treat breast cancer has demonstratedremar􀁍able benefits to cancer patients. 􀀰anoparticle􀀏based treatmentsfor cancer therapy represent a promising strategyto enhancetherapeutic outcomes by reducing off􀀏target side effects. 􀀹edevelopedseveral techniques to prepare silica nanoparticles hollo􀁙 􀀊Si􀀱2􀀰􀀲s􀀋 that carrying on the surface T􀀼 􀀊T􀀼􀀰􀀲s􀀋. This is ananoparticle able to carry drugs or immunomodulatory moleculesin the hollo􀁙 and it 􀁙ould be directed to the tumor microenvironmentby the presence of the antibody. As it has been sho􀁙n thatneutrophils may play a crucial role in the tumor microenvironmentincluding both promoting or inhibiting tumor gro􀁙th, 􀁙e evaluatedthe effect of this ne􀁙 tool on thesecells. 􀀹e evaluated theproduction of T􀀩F􀁅 as protumor 􀀰􀀔 phenotype and theproductionof 􀀫L􀀏􀀓􀁅 and nitric oxide 􀀊􀀰􀀱􀀋 as phenotype 􀀰􀀓 antitumor to inducingimmunogeniccell death. 􀀫n order to study the effect of 􀀰􀀲 onneutrophils, thecells 􀁙ere incubated for 􀀖 h and the supernatants􀁙ere obtained. 􀀰eutrophils in presence of Si􀀱2NPs produced highconcentrations of 􀀰􀀱 and 􀀫L􀀏􀀓􀁅 compared to control. Furthermore,concentrations of T􀀩F􀁅 􀁙ere not significant. 􀀯oreover, the mAbT􀀼 produced a significant increase of 􀀫L􀀏􀀓􀁅, a slight increase ofT􀀩F and similar values of 􀀰􀀱 􀁙ith respect to control cells. Finally,􀁙e evaluated T􀀼􀀰􀀲s observing similar levels of T􀀩F􀁅, IL-1􀁅 and􀀰􀀱 in comparison to control cells.These results demonstrate thatT􀀼􀀰􀀲S does not activate the protumor 􀀰􀀔 phenotype. Therefore,T􀀼􀀰􀀲s could be a safe tool for the treatment of illness by recognizingspecific tumor cells and transporting effectors molecules.