Near-infrared induced phase-shifted ICG/Fe3O4 loaded PLGA nanoparticles for photothermal tumor ablation

<jats:title>Abstract</jats:title><jats:p>Near-infrared (NIR) laser-induced photothermal therapy (PTT) uses a photothermal agent to convert optical energy into thermal energy and has great potential as an effective local, minimally invasive treatment modality for killing cancer cells. To improve the efficacy of PTT, we developed poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) encapsulating superparamagnetic iron oxide (Fe<jats:sub>3</jats:sub>O<jats:sub>4</jats:sub>), indocyanine green (ICG), and perfluoropentane (PFP) as synergistic agents for NIR laser-induced PTT. We fabricated a novel type of phase-shifting fluorescent magnetic NPs, Fe<jats:sub>3</jats:sub>O<jats:sub>4</jats:sub>/ICG@PLGA/PFP NPs, that effectively produce heat in response to NIR laser irradiation for an enhanced thermal ablation effect and a phase-shift thermoelastic expansion effect, and thus, can be used as a photothermal agent. After <jats:italic>in vitro</jats:italic> treatment of MCF-7 breast cancer cells with Fe<jats:sub>3</jats:sub>O<jats:sub>4</jats:sub>/ICG@PLGA/PFP NPs and NIR laser irradiation, histology and electron microscopy confirmed severe damage to the cells and the formation of many microbubbles with iron particles at the edge or outside of the microbubbles. <jats:italic>In vivo</jats:italic> experiments in mice with MCF-7 tumors demonstrated that Fe<jats:sub>3</jats:sub>O<jats:sub>4</jats:sub>/ICG@PLGA/PFP NPs could achieve tumor ablation upon NIR laser irradiation with minimal toxicity to non-irradiated tissues. Together, our results indicate that Fe<jats:sub>3</jats:sub>O<jats:sub>4</jats:sub>/ICG@PLGA/PFP NPs can be used as effective nanotheranostic agents for tumor ablation.</jats:p>