Monitoring of release of cargo from nanocarriers by MRI/MR spectroscopy (MRS): significance of T2/T2* effect of iron particles.

To monitor the release of cargo molecules from nanocarriers, a novel MRI/MRS technique was developed and tested. This novel approach uses a simultaneous encapsulation of superparamagnetic iron oxide (SPIO) nanoparticles and either a gadolinium (Gd)-based paramagnetic contrast agent, Gd-diethylenetriamine pentaacetic acid bismethylamide(GdDTPA-BMA), for MRI, or an anticancer agent, 5-fluorouracil (5-FU), for MRS. These agents have significantly different diffusion properties due to their different molecular sizes. Strong negative signal enhancement due to the T(2) effects of SPIO dominates the positive T(1) contrast generated by GdDTPA-BMA when SPIO and GdDTPA-BMA are in close proximity (intact form). Positive T(1) contrast becomes evident upon release of GdDTPA-BMA from the carrier once the distance between GdDTPA-BMA and SPIO molecules is beyond the T(2) enhancement range. Similarly, intact nanocarriers loaded with 5-FU and SPIO have a broad (19)F resonance line because line-width is inversely proportional to T*2, while free 5-FU appears as a narrow resonance line once it is released from the liposomes. This technique allowed monitoring of the release of cargo molecules from liposomes encapsulating both SPIO and either GdDTPA-BMA or 5-FU by MRI/MRS in vitro using 2% agarose gel phantoms. Experimental results demonstrate successful demarcation of the released cargo molecules vs. encapsulated molecules.