Abstract 380: Magnetic nanoplatforms for tumor targeting, imaging and energy delivery

We have developed magnetic nano-liposomes (MNL), incorporating superparamagnetic iron oxide nanoparticles (SPION), that are versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. MNL are prepared with a formuation of DPPC:DOTAP:CHOL and DOPE-PEG5000. Incorporation of SPIONs results in MNL with mean diameter of 150-250 nm. MNL are easily taken up by B16-F10 melanoma, HUMVEC-D and breast cancer cell lines. They preferentially target the tumor vasculature as shown in a dorsal skin fold chamber using fluorescently labeled MNL. MNL display superparamagnetic response that is essential for magnetic targeting, MR contrast enhancement and magnetic heating. MNL was administrated to SCID mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre-injection and post-injection MR images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by 111In labeled MNL and amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations. We have shown that tumor signal intensities in T2 weighted images decreased an average of 20±5% and T2* values decreased and average of 14±7ms in the absence of magnetic targeting. This compares to an average signal decrease of 57±12% and a decrease in T2* relaxation times of 27±8ms with the aid of external magnet showing up to 2-fold greater accumulation by magnetic targeting. 111In radio-labeled MNL have been shown to enable multi-modal imaging in vivo using MRI and SPeCT/CT. The images show that an MNL bolus injected intra-tumorally was retained in the tumor 24 hours after injection. Application of a magnetic field enables redistribution of the MNL in the tumor. These MNL are also responsive to ac magnetic fields applied using a Copper coil at 360 kHz and 170A driving current. Both hyperthermia (upto 45C) and thermo-ablative temperatures upto 90C were achieved in 10 – 30 minutes ex vivo in buffer. The results indicate high efficiency for magnetic heating using MNL (Specific Absorption Rate ∼ 104 W/kg) and demonstrate the capability to couple ac magnetic fields to MNL to achieve any set of temperatures needed for hyperthermia and thermal ablation. To date there are no truly theranostic platforms that have been approved for clinical use that combine targeting, thermal heating and MRI imaging capabilities. Existing FDA approved magnetic nanoparticle formulations like ferridex and ferumoxytol, are optimized for MR imaging, and have not been shown to be usable for thermal therapy.The MNL platform is a novel nanoplatform combining multi-modal imaging capabilities, with magnetic targeting and thermal therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2011-380