Dual targeted magnetic photosensitive liposomes for photothermal/photodynamic tumor therapy

In this work, we prepared a nano-vehicle for dual targeted (magnetic and ligand) and dual mode (photothermal/photodynamic) cancer therapy. For this purpose, magnetic photosensitive liposomes (MPLs) from 1,2-distearoyl-sn-glycero-3-phosphocholine, dimethyldioctadecyl ammonium bromide (DDAB) and cholesterol were prepared using solvent evaporation/hydration technique to encapsulate the photosensitizer indocyanine green (ICG) and citric acid-coated MNPs (CMNPs). Hyaluronic acid-polyethylene glycol (HA-PEG) was coated to the MPLs by self-assembly of HA-PEG on liposome surface through ionic interactions between negatively charged HA and positively charged lipid DDAB to fabricate HA-PEG-MPLs with ∼220 nm particle size. The HA-PEG-MPLs aqueous solution showed highly efficient photothermal effects as the solution temperature reaches 45 °C in 3 min after exposure to near infrared (NIR) 808 nm laser at 2 W/cm2. The in vitro cell culture experiments after treating human glioblastoma cells (U-87MG) with HA-PEG-MPLs confirmed enhanced cytotoxicity after 4 min exposure to NIR laser. A xenograft tumor model from subcutaneously implanted U87MG cells in nude mice demonstrated accumulation of HA-PEG-MPLs at tumor sites. By combination with successive NIR laser treatment, tumor growth could be prevented and the tumor volume at the end of treatment was 12.7% that of the control. Excellent and consistent anti-tumor efficacy with laser + HA-PEG-MPLs treatment was also demonstrated from the survival rates of animals, in vivo bioluminescence imaging and histology of tumor sections.