LAUSR

Simple Summary Despite tremendous efforts in finding new therapeutic strategies and promoting screening programs to increase early diagnosis, breast cancer is still a major cause of death in the female worldwide population. Preclinical and clinical evidence have shown that nanotechnologies can significantly contribute to improving both therapeutic and diagnostic aspects. This is particularly true for human epidermal growth factor receptor-2 (HER-2) overexpressing (HER-2+) breast cancer, where recurrence rates and drug resistance still make it one of the most aggressive breast cancer subtypes, despite the development of promising targeted therapies. The aim of this review is to provide an update on the most promising nanoparticle-based approaches developed in the last decade in the context of HER-2-positive breast cancer therapy and diagnosis. Abstract Human epidermal growth factor receptor-2 (HER-2) overexpressing breast cancer is a breast cancer subtype characterized by high aggressiveness, high frequency of brain metastases and poor prognosis. HER-2, a glycoprotein belonging to the ErbB receptor family, is overexpressed on the outer membrane of cancer cells and has been an important therapeutic target for the development of targeted drugs, such as the monoclonal antibodies trastuzumab and pertuzumab. These therapies have been available in clinics for more than twenty years. However, despite the initial enthusiasm, a major issue emerged limiting HER-2 targeted therapy efficacy, i.e., the evolution of drug resistance, which could be tackled by nanotechnology. The aim of this review is to provide a first critical update on the different types of HER-2-targeted nanoparticles that have been proposed in the literature in the last decade for therapeutic purposes. We focus on the different targeting strategies that have been explored, their relative outcomes and current limitations that still need to be improved. Then, we review the nanotools developed as diagnostic kits, focusing on the most recent techniques, which allow accurate quantification of HER-2 levels in tissues, with the aim of promoting more personalized medicinal approaches in patients.