Use of ultrasound with magnetic field for enhanced in vitro drug delivery in colon cancer treatment

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ug delivery systems (DDSs) have been developed to target tumor cells by releasing active biomolecules at the specific site of infection, thus eliminating the side effects of anticancer drugs. However, DDSs are generally limited by high drug dosage, biobarriers, poor target recognition, etc. To address these deficiencies, we propose a new noninvasive method consisting of exposing the cancer cells to a combination of low-intensity pulsed ultrasound (LIPUS) and static magnetic field (SMF). This combined treatment found to negatively regulate colon cancer cell (HCT116) activities in vitro by altering their cell membrane potential and permeability thus increased the DDS efficacy by 40%. The treated cancer cell membrane became hyperpolarized leading to cancer cell death. The combination treatment (LIPUS 1 SMF) restricted the cancer cell proliferation to 16 and 5% in the presence of bare anticancer drug and DDS, respectively, in 72 h, which is almost 40% higher than that observed without the treatment. The acceleration of cancer cellular inhibition was confirmed by the significant increase in the apoptosis of the cell exposed to the LIPUS 1 SMF treatment. The observed improvement is believed to be due to changes in the cell membrane stability/permeability as a result of mechanical (20–22 kPa) and electrical (19–23 lV/cm) stimuli generated during the LIPUS 1 SMF treatment. I. INTRODUCTION

Generally the cancer treatment involves chemotherapy along with surgery, radiation therapy, or biological therapy. Chemotherapy can affect the normal cells leading to damage of skin, hair, lining of digestive system, and other organs.1 It also affects the bone marrow thus increasing the risk of developing infections which are often life threatening.2 Likewise, the high dose of anticancer drugs is highly detrimental to the patients’ immunity.3 Therefore, numerous external stimuli, such as ultrasound, magnetic field, light, are currently being explored as therapeutics in conjunction with drug delivery systems (DDSs) for cancer treatment.4 Important mechanisms associated with these external stimuli, in inhibiting cancer cell growth, include hyperthermia, controlled drug release, and changing membrane permeability.5,6 For example, ultrasound has been used to generate reactive oxygen species (ROS) inside the tumor of mice, which was administered with TiO2-based nanoparticles (NPs), and suppressed the tumor growth.7 Furthermore, inherent electrical characteristics of cells have been used to inhibit cancer cells using external electrical fields.8 Some of these external stimuli have also a)

Address all correspondence to this author. e-mail: [email protected] DOI: 10.1557/jmr.2018.43

been used to alter membrane permeability thereby improving the efficiency of DDS-based cancer treatment.9 The use of DDS, which typically consists of NPs loaded with anticancer drugs, for cancer treatment is aimed at controlling the rate of drug delivery thereby providing sustained therapeutic activity at the targeted tissue for better therapeutic effect of drugs with m