HER-2-Targeted Nanoparticles for Breast Cancer Diagnosis and Treatment

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.

Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy

“…In addition, DPDS was reported to be toxic to the hematopoietic system. 42 Fortunately, with the advantages of nanocarriers, DPDS can be encapsulated into nanocarriers conjugated with ligands such as growth factors that bind to the membrane receptor Her2 or other tumor antigens, [43][44][45] which could increase the specificity and cytotoxicity in breast cancer.…”

Nanodelivery systems: An efficient and target‐specific approach for drug‐resistant cancers

“…It has already been used as a candidate for cancer therapy 61 . For instance, therapies targeting the human epidermal receptor 2 (HER2) are typically effective in HER2‐positive mammary and gastric cancers 62,63 . Therefore, a promising approach for medication delivery targets cancer cells that overexpress the EGFR receptor by using customized ligands that adhere to EGFR in NPs.…”

Classic and New Markers in Diagnostics and Classification of Breast Cancer

“…As an advantage, this abnormal tumour-selective endothelial permeability allows gradual accumulation of NPs or NPs-treated drugs in cancer tissue that is further facilitated by defective lymphathetic drainage in the tumours and lower-rate of NPs-phagocytic removal as opposite to the obvious size of particles (>100 nm in diameter). While passive targeting uses the above inherent physical properties, active nanocarriers further improve tumour-lineage specific targeting by using NPs with antibodies or ligands directed towards specific tumour antigens, e.g., anti-HER2 antibody-PEG liposomes targeting HER+ BC [ 91 ]. Inorganic, mostly metal based NPs with silver (Ag), platinum (Pt), gold (Au), Au–Ag alloy, Au–gadolinium (Gd) cores appeared to suitable contrast agents (CAs) that provide better signal-difference-to-noise-ratio over classical CAs (e.g., iodine based) when analysing BCs in naturally dense breast tissue using mammographic imaging techniques such as computed tomography (CT) (e.g., Ag Au NPs, near-infrared fluorescence (NIRF) (e.g., Au and AgNPs) or contrast enhanced dual-energy mammography (DEM) (e.g., AuNPs) [ 92 ].…”