Hybrid Nanoparticles Targeted by Antitumor Antibodies and Emitting Alpha-particles
I.V. Resheto, S.M. Deev, D.Y. Chuvilin, V.Y. Panchenko, S.S. Sukharev, E.A. Streltsova
P.A. Hertzen Moscow Research Oncological Institute (MROI), RU
Keywords: tumor-targeted nanoparticles, biodistribution, AFM, radiopharmaceuticals
Abstract:We describe a new therapeutic nanoparticle’s design, which consists of three parts: targeting, effecter and linker. Targeting part: an anti-HER2/neu mini-antibody-barnase fusion protein (4D5 scFv-barnase-His5). The anti-HER2/neu mini-antibody could be used to deliver barnase to HER2/neu-positive cells and provide its penetration into the target cells, as HER2/neu is a ligand-internalizing receptor. This expression vector has potential applications to both gene and antibody therapies of cancer, because many tumor cells are HER2/neu-positive, breast cancer for example. Effecter: Actinium-225 is used in present work as a generator for alpha-particle therapy: it decays with a 10-day half-life and generates three alpha-particle-emitting daughters. Linker: synthetic strategies for construction of hybrid nanoparticles under study based on chelating agents. It was proven by experiments with breast cancer cells in-vitro, that anti-HER2/neu mini-antibody created do conjugate effectively with tumor cells. Stability of nanoparticles was proven by AFM measurements in vitro. Hybrid nanoparticles designed are being evaluated by in-vivo studies in animals (nude mouse) model. Reliable clinical improvement in terms of Survival Analysis was noticed when using nanoparticles for model tumors therapy. Our results form basics for creation of a new targeted radiopharmaceuticals.