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 (As3+)-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 As3+, the active form of ATO, and Mn2+, 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.
Highlights
One emerging nanotechnology with enormous potential for image-guided anticancer therapy involves the hybrid of imaging and therapeutic agents into a single nanostructure
arsenic trioxide (ATO) is actively loaded into the core of liposomes, where the pre-entrapped manganese acetate complexes with ATO, as clearly seen in the TEM images as the electron-dense precipitates in the liposomal cores (Fig. 2b)
A number of traditional chemotherapeutic agents including doxorubicin, topotecan and platinum have been successfully entrapped in liposomes by forming drug-metal complex[32,33]
Summary
One emerging nanotechnology with enormous potential for image-guided anticancer therapy involves the hybrid of imaging and therapeutic agents into a single nanostructure (so-called theranostics). Recent studies by us and others have shown that the harsh tumor microenvironment characterized by hypoxia, acidosis and oxidative stress causes redistribution of PS from the inner to the outer membrane leaflet of tumor endothelial cells and tumor cells in various cancers including GBM23–25. These PS-exposed tumor cells are found to be viable and not subjected to apoptotic process. By functionalizing the PEGylated liposomes with the F(ab’)[2] fragments of PGN635, a novel human monoclonal PS-targeting antibody, our initial applications have clearly demonstrated that the PS-targeted nanoprobes of optical/ MRI contrast agents provided sensitive and specific tumor imaging[21,22]. Longitudinal MRI was applied to monitor the imaging contrast changes, aiming to achieve MRI-guided delivery and release of ATO
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
