Current Molecular Medicine               N.M. Salkho a , R.Z. Turki a , O. Guessoum b , A.M. Martins a , R.F. Vitor a and G.A. Husseini* ,a a Department of Chemical Engineering, American University of Sharjah, Sharjah, UAE; b Department of Chemistry, Biology and Environmental Science, American University of Sharjah, Sharjah, UAE Abstract: The initial uses of ultrasound waves in the medical field were limited to the thermal ablation of solid tumors and as a diagnostic tool. Recent advances at the preclinical stage have allowed the use of ultrasound as a powerful tool to improve drug delivery when the agent is administered encapsulated inside a nanoparticle. This spatial and temporal control of drug release, using a non-invasive modality, is a promising approach to decrease the side effects of conventional chemotherapy in cancer treatments, as it reduces the interaction of the anti-neoplastic agent with healthy tissues. In this review, we explain the physics of ultrasound, introduce and discuss several examples on the use of nanoparticles as drug carriers, with a focus on liposomes. Examples of in vitro and in vivo studies are presented and discussed. A R T I C L E H I S T O R Y Received: November 26, 2017 Revised: March 28, 2018 Accepted: March 31, 2018 DOI: 10.2174/1566524018666180416100142 Keywords: Cancer, liposomes, drug delivery, ultrasound, drug release, anti-neoplastic agent. 1. INTRODUCTION The development of effective cancer therapy alternatives remains an unpaired challenge. The World Health Organization reported 8.2 million deaths related to cancer in 2012, and predicts a rise of about 70% in new cases the next two decade [1]. Thus, the development of novel biomedical technologies and the improvement of cancer physiopathology knowledge are vital. Many treatment methods are commonly used and known, i.e., chemotherapy, surgery (in early cancer stages), hormonal therapy (to decrease or completely impair the production of hormones that stimulate the tumor growth) and targeted therapy (the focus of this paper). Traditional chemotherapeutic drugs are largely involved in the inhibition of cell division and their side effects include damaging normal/healthy cells that divide rapidly and are thus sensitive to anti-mitotic drugs (for example, cells in the bone marrow, digestive tract or hair follicles). The low efficiency of drug delivery to the tumor tissues is also an issue which increases toxicity to healthy cells and remains hampered by the difficult penetration of the drug in the vicinity of the cells that cause the disease. In fact, the pharmacokinetics of the chemotherapeutical drug is usually very poor, with a low percentage of the total amount of administrated drug reaching the tumor tissue. The main reason for this is the poor and heterogeneous vascularization of *Address correspondence to this author at the Department of Chemical Engineering, American University of Sharjah, P.O. Box: 26666, Sharjah, UAE; Tel/Fax: +971-6-515 2970, +971-6-515 2979; E-mail: ghusseini@aus.edu tumors and the high fluid pressure of the interstitial tissue of the tumors [2]. In an attempt to decrease the side effects of chemotherapy on healthy tissues, researchers developed nanoparticles to carry drugs and preferably extravasate into tumor tissue due to the enhanced permeability and retention (EPR) effect [3]. Because of its specificity, low toxicity, solubility in biological fluids, and immunostimulatory properties, targeted therapy using synthetic polymer nanoparticles has fewer side effects than traditional therapy with the additional advantage that various drugs can be encapsulated for all types of cancer [4]. Several nanoparticles have been studied for this purpose, such as micelles, dendrimers, solid lipid nanoparticles, and liposomes, among others. Liposomes offer the advantage that they are similar to the cellular membrane, being composed of a lipid bilayer surrounding an aqueous core where hydrophilic drugs can be encapsulated [5]. This reduces undesired effects such as being captured by the immune system and it also allows the fusion of the liposomal and the cell membranes, and the release of the anti-neoplastic drugs intracellularly. Additionally, it is possible to enhance the specificity of these nanoparticles to cancer cells, by attaching ligands to their surface, and making use of the fact that cancer cells usually overexpress receptors for several ligands such as folic acid [6]. This results in a preferential targeting of these drug carriers to the cancer cells and reduces their impact on healthy tissues and organs. 1875-5666/17 $58.00+.00 © 2017 Bentham Science Publishers REVIEW ARTICLE Liposomes as a Promising Ultrasound-Triggered Drug Delivery System in Cancer Treatment Send Orders for Reprints to reprints@benthamscience.ae 668 Current Molecular Medicine 2017, 17, 668-688