Ultrasound-triggered herceptin liposomes for breast cancer therapy

Abstract

The functionalization of liposomes with monoclonal antibodies is a potential strategy to increase the specificity of liposomes and reduce the side-effects associated with chemotherapeutic agents. The active targeting of the Human Epidermal growth factor Receptor 2 (HER2), which is overexpressed in HER2 positive breast cancer cells, can be achieved by coating liposomes with an anti-HER2 monoclonal antibody. In this study, we synthesized calcein and Doxorubicin-loaded immunoliposomes functionalized with the monoclonal antibody Trastuzumab (TRA). Both liposomes were characterized for their size, phospholipid content and antibody conjugation. Exposing the liposomes to low-frequency ultrasound (LFUS) triggered drug release which increased with the increase in power density. Trastuzumab conjugation resulted in enhancing the sensitivity of the liposomes to LFUS. Compared to the control liposomes, TRA-liposomes showed higher cellular toxicity and higher drug uptake by the HER2 + cell line (SKBR3) which was further improved following sonication with LFUS. Combining immunoliposomes with LFUS is a promising technique in the field of targeted drug delivery that can enhance efficiency and reduce the cytotoxicity of antineoplastic drugs.

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

“…The first conventional liposomes mainly adopt the stealth strategy to escape capture by the reticuloendothelial system (RES) and to prolong blood circulation [ 48 ]. Polyethylene glycol (PEG) is the most widely used material for the stealth modification of the liposomes, thus the PEGylated liposomes are also called stealth liposomes [ 49 ]. Furthermore, stealth liposomes can achieve passive targeting by virtue of the EPR effect [ 50 ].…”

Comprehensive review on ultrasound-responsive theranostic nanomaterials: mechanisms, structures and medical applications

“…Low-intensity focused US (LIFU) was used to trigger the release of drugs from liposomes. Trastuzumab-functionalized liposomes showed higher cellular toxicity and higher drug uptake by the HER2-positive cell line and the addition of LIFU further improved the therapeutic outcomes [ 260 ]. In a similar study, calcein‐loaded liposomes functionalized with transferrin were used for the targeting of HeLa cells.…”

“…However, their phagocytosis in the blood circulation is still challenging [252]. Liposomes can also be targeted via surface ligands in order to maximize the efficacy of cargo delivery and minimize systemic side effects [260][261][262].…”

Development of Liposome-Based Immunoassay for the Detection of Cardiac Troponin I

“…Liposomes are non-toxic, biocompatible nano-vehicles formed by the self-assembly of phospholipids into a bilayer, creating an inside aqueous compartment that can be loaded with water-soluble compounds, such as fluorescent dyes (Scheme 1). The outside layer of the phospholipid can be chemically functionalized to be brandished with different moieties, such as ligands or antibodies [45][46][47][48][49]. On the other hand, calcein is a water-soluble fluorescent dye that has a self-quenching property at high concentrations, and it can be loaded inside liposomes at high concentrations [46,50].…”