Angiopep-2/IP10-EGFRvIIIscFv modified nanoparticles and CTL synergistically inhibit malignant glioblastoma

Abstract

Preparation of agents that can successfully traverse the blood-brain-barrier (BBB) is a key challenge in brain cancer therapeutics. In this study, angiopep-2 was used as a brain-targeting peptide for preparing multifunctional Angiopep-2-modified poly nanoparticles, angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles. In vitro experiments showed a greater uptake of Angiopep-2 modified nanoparticles, also angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles by bEnd.3 cells versus nanoparticles and nanoparticles modified by IP10-EGFRvIIIscFv. Angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles accumulated in brain tissue after intravenous injection and recruited activated CD8 ⁺ T lymphocytes to location of glioblastoma cells. In vivo experiments to assess anti-glioblastoma effect of angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles showed significantly reduced tumor volume in angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles ⁺ CD8 ⁺ cytotoxic T lymphocytes group versus in NPs modified by IP10-EGFRvIIIscFv ⁺ CD8 ⁺ cytotoxic T lymphocytes, CD8 ⁺ cytotoxic T lymphocytes, Angiopep-2 modified nanoparticles ⁺ CD8 ⁺ cytotoxic T lymphocytes, angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles and PBS groups. Leukocytes infiltrated in brain tissues showed strong anti-glioblastoma activity in angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles ⁺ CD8 ⁺ cytotoxic T lymphocytes treated mice. Thus, angiopep-2 and IP10-EGFRvIIIscFv fusion protein modified nanoparticles may be useful for brain-targeted delivery and recruitment of activated CD8 ⁺ T lymphocytes to glioblastoma cells.