title: Convertible MRI contrast: Sensing the delivery and release of anti-glioma nano-drugs.
abstract: 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 T2-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 T1 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.
authors.affiliation: Radiology, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Radiology, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Radiology, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Mason
authors.affiliation: Radiation Oncology, Mayo Clinic, Rochester, MN.
authors.forename: Jann N
authors.initials: JN
authors.lastname: Sarkaria
authors.affiliation: Radiology, UT Southwestern Medical Center, Dallas, TX.
authors.forename: Dawen
authors.initials: D
authors.lastname: Zhao
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry / Q000494:pharmacology; D011859:Radiography
chemical_list: D001152:Arsenicals; D003287:Contrast Media; D010087:Oxides; D008345:Manganese; D000077237:Arsenic Trioxide