Development of New Hollow Mesoporous Silica Nanoparticles Coated with mAb Trastuzumab to Treat Breast Carcinoma

ROMINA MITAROTONDA; MARTIN F DESIMONE; MAURICIO DE MARZI; MARÍA EUGENIA DÍAZ

San Francisco

Congreso; Federation of Clinical Immunology Societies; 2018

Federation of Clinical Immunology Societies, FOCIS

Breast carcinoma is the most frequent cancer in women with more than one million new cases reported in the USA each year. Although current therapeutic interventions have increased the 5-year survival rate for women with the disease, there is still an urgent need to develop new strategies to fight breast cancer. Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising carriers for effective drug delivery due to their large surface area, high volume for drug loading and excellent biocompatibility. For this reason, we previously developed and described hollow mesoporous silica nanoparticles with antibody Trastuzumab (HMSNs-TZ) in its surface. These NPs were then modified with Eudragit (HMSNs-TZ-RL) in order to regulate drug release. The aim of this work was to investigate the effect of HMSNs-TZ-RL carrying doxorubicin on BT474 spheroids, as an in vitro model of human breast carcinoma. First, the intracellular delivery of HMSNs-TZ was evaluated. Spheroids were treated with the NPs (20 μg/mL) for 6 h. Subsequently, the cells were washed extensively with PBS, fixed in 4% paraformaldehyde, and visualized immediately. We observe the entry of a large number of nanoparticles inside the tumor. HMSNs-TZ modified on their surface with Eudragit allowed the release of doxorubicin with the change of tumoral pH. Therefore, we evaluated the effect of these NPs on BT474 spheroids. Our results showed a significant decrease in tumoral proliferation when cells were incubated in the presence of HMSNs-TZ-RL. There was also a significant increasein HSP-70 levels together with an increase of apoptotic cells.