Alpha-particle emitters targeted by specific antitumor antibodiesстатья
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Дата последнего поиска статьи во внешних источниках: 8 января 2017 г.
Аннотация:Background: Alpha-particle emitters as part of hybrid nanoparticles hold
great promise as therapeutics for micrometastatic disease. Here we
describe a new therapeutic nanoparticle’s design, which consists of three
parts: targeting, effecter and linker.
Materials and methods: Targeting part: an anti-HER2/neu mini-antibodybarnase
fusion protein (4D5 scFv-barnase-His5). The anti-HER2/neu miniantibody
could be used to deliver barnase to HER2/neu-positive cells and
provide its penetration into the target cells, as HER2/neu is a ligandinternalizing
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: Tumor targeted alpha-particles can result in high cancer-cell
killing with minimal normal-tissue irradiation because of their high energy
deposition and short range. 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.
Results: 1. It was proven by experiments with breast cancer cells in-vitro,
that anti-HER2/neu mini-antibody created do conjugate effectively with tumor cells.
2. Stability of chelating agents chosen complex with different
metals was proven.
3. Stability of chelating agents complex with mini-antibody created was
also proven (in-vitro). Hybrid nanoparticles designed are being evaluated
by in-vivo biodistribution studies in animal (rats) models.
Conclusions: Tumor-targeted nanoparticles with conjugated specific
antitumor antibodies are promising tools for the reduction of malignant
tumors. Our results form basics for creation of new targeted radiopharmaceuticals.