Ultrasound-triggered herceptin liposomes for breast cancer therapy

Amal Elamir,Debasmita Mukhopadhyay,Nour Al Sawaftah,Mohammad H Al-Sayah,Nahid Awad,Waad Abuwatfa,Vinod Paul,Ghaleb A Husseini,Saniha Ajith

doi:10.1038/s41598-021-86860-5

Amal Elamir, Debasmita Mukhopadhyay + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-86860-5

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Journal: Scientific Reports	Publication Date: Apr 6, 2021
Citations: 55	License type: open-access

Affiliation: American University of Sharjah

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.

Highlights

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
Dynamic light scattering (DLS) measurements were performed to ensure the formation of liposomes and to measure the size of both types of synthesized liposomes
The results showed a higher F-value compared to F critical, as well as a p-value lower than the standard alpha value of 0.05, which indicated that the two types of nanoparticles had statistically different radii

Summary

Introduction

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. TRA can prevent HER2 hetero-dimerization and stop tumor development cell signaling via several mechanisms, including reduced PI3K/Akt signaling, enhanced degradation of HER2 receptors, and antibody-dependent cellular cytotoxicity (ADCC). This drug is considered a HER2 receptor antagonist[15,16,17]. Anti-HER2 immunoliposomes combine the tumor-targeting properties of mAbs, with the drug delivery properties and multi-drug resistance (MDR) mitigation ability of sterically stabilized liposomes encapsulating chemotherapeutic agents; offering prolonged inhibition of the HER2 pathway across multiple lines of treatment which will hopefully result in continued improvements in outcomes for HER2-positive breast cancer p atients[18,19,23]

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Conclusion