Abstract

In-vitro Application of Doxorubicin Loaded Magnetoplasmonic Thermosensitive Liposomes for Laser Hyperthermia and Chemotherapy of Breast Cancer

Mohammad E Khosroshahi, Lida Ghazanfari, Zahra Hassannejad and Steven Lenhert

We describe doxorubicin loaded magnetoplasmonic thermosensitive liposomes (MPTL-DOX), which are designed to combine features of magnetic drug targeting and laser hyperthermia-triggered drug release. The synthesized magnetite/gold nanoshells are stabilized using polyvinyl pyrolidone (PVP) with mean crystallite size of 15.8 ± 3.5 nm. The liposome formulation DPPC:cholesterol:DSPE-PEG2000 at 80:20:5 molar ratio shows DOX release of less than 5% at 37°C following 24 h incubation. MPTL-DOX shows encapsulation efficiencies of about 95% and 74% for DOX and magnetoplasmonic nanoshells (MPNS), respectively. The MPTL-DOX formulation displays a desired temperature sensitivity with 65% and 100% DOX release following laser irradiation and then 24 h incubation at 37°C, respectively. The rate of DOX release from liposome using this formulation is 0.09 which was obtained by heating to 43°C, and agrees well with the first kinetic model. A temperature rise between 4-12°C was achieved for MNS using 25 μg/ml and 300 μg/ml after 400 s respectively. For cytotoxicity measurement, one untreated (control) and two treatment groups are studied. The first treatment groups are: with MPNS only, with MPTL only, and laser irradiation only. The second treatment groups are: laser hyperthermia using MPTL, MPTL with magnetic field (MF), MPTL-DOX, and MPTL-DOX with MF. MPTL-DOX is targeted to breast cancer cell lines (MCF-7 cells) under a permanent magnetic field and exhibits a substantial increase in cytotoxicity and apoptotic effects. The results suggest that externally guided drug targeting can trigger drug release using an exogenous absorber in laser hyperthermia which can be used advantageously for thermo-chemotherapy of cancers.