Improved chemotherapeutic delivery to brain metastases with targeted nanoparticles in preclinical breast cancer brain metastasis models

Abstract

Brain metastases present an increasing challenge to long-term survival for HER2-amplified breast cancer patients. While HER2 targeted therapies effectively control systemic metastases, they are largely ineffective against brain metastases due to their inability to cross the blood-brain barrier. We have recently demonstrated that brain uptake of targeted nanoparticles can be increased by adding an acid-cleavable linkage between transferrin (Tf) and the nanoparticle core [1]. Our lab has also developed a method for assembling targeted nanoparticles by complexing diol-containing polymerdrug conjugates and boronic acid-containing targeting agents [2]. Here, we report the first efficacy results of targeted nanoparticles formed via this assembly strategy in a preclinical model of breast cancer brain metastasis.