Convertible MRI contrast: Sensing the delivery and release of anti-glioma nano-drugs

There is considerable interest in developing nanohybrids of imaging contrast agents and drugs for image-guided drug delivery. We have developed a strategy of utilizing manganese (Mn) to enhance the nano-encapsulation of arsenic trioxide (ATO). Formation of arsenite (As(3+))-Mn precipitates in liposomes generates magnetic susceptibility effects, reflected as dark contrast on T(2)-weighted MRI. Intriguingly, following cell uptake, the As-Mn complex decomposes in response to low pH in endosome-lysosome releasing ionic As(3+), the active form of ATO, and Mn(2+), the T(1) contrast agent that gives a bright signal. Glioblastoma (GBM) is well known for its high resistance to chemotherapy, e.g., temozolomide (TMZ). Building upon the previously established phosphatidylserine (PS)-targeted nanoplatform that has excellent GBM-targeting specificity, we now demonstrate the effectiveness of the targeted nanoformulated ATO for treating TMZ-resistant GBM cells and the ability of the convertible Mn contrast as a surrogate revealing the delivery and release of ATO.