Abstract 2132: Anti-vascular inflammatory nanoparticles inhibit tumor progression and metastasis through vascular normalization

Abstract

Abstract Vascular networks in cancer are structurally and functionally abnormal. Abnormal blood vessel development in cancer plays an important role in cancer growth and metastasis, and blocks delivery of chemotherapeutic drugs. Recent studies have revealed that the normalization of abnormal tumor vasculature is one of the promising approaches to treat cancer. Inflammatory microenvironment is one of the newly focused hallmarks of cancer, and tumor vasculature has similar features to that of inflammatory vessels. Thus, vascular inflammation is emerged as an attractive target for cancer treatment. We hypothesized that amelioration of vascular inflammation in tumor may induce vascular normalization leading to the inhibition of tumor progression and metastasis. Here, we investigated the function of ant-vascular nanoparticles in tumor growth and metastasis in LLC allograft tumor models and MMTV-PyMT, spontaneous breast tumor models using TFG and TFMG which are engineered a protein-cage nano-particle (ferritin) with both EPCR-targeting peptides (γ-carboxyglutamic acid (Gla) domain of protein C) and PAR-1-activating peptides (TRAP) of thrombin on its surface. As a result, tumor growth was significantly inhibited in the nanoparticle-injected group, and the lymph node metastasis was also decreased in both animal models. It has been found that the survival rate of the nanoparticle-injected group was prolonged. TFG and TFMG normalized abnormal tumor vasculature, that is, pericytes coverage in vasculatures was significantly increased but the hypoxic regions was decreased in the nanoparticle injected group. Furthermore, when the experiment was conducted by administering cisplatin and nanoparticles together in the LLC allograft tumor model, the tumor size was synergistically increased in the case of the nanoparticle and cisplatin combination administration compared to the cisplatin alone group. Taken together, anti-vascular inflammation nanoparticles with anti-vascular inflammatory properties normalized the abnormal blood vessels and inhibited tumor formation and metastasis. It is suggested that inducing normalization of cancer blood vessels by improving the inflammatory state of blood vessels may be a promising therapeutic method for effective cancer treatment. Citation Format: Young Sun Choi, Soo Hyun Kang, Jong-Sup Bae, In-San Kim, You Mie Lee. Anti-vascular inflammatory nanoparticles inhibit tumor progression and metastasis through vascular normalization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2132.