An Asymmetrical Polymer Vesicle Strategy for Significantly Improving T1 MRI Sensitivity and Cancer-Targeted Drug Delivery

Traditional T 1 magnetic resonance imaging (MRI) contrast agents such as diethylenetriaminepentacetatic acid (DTPA) chelated gadolinium [Gd(III)] have poor sensitivity, leading to a risk of accumulated toxicity in vivo . To significantly improve the sensitivity of a T 1 MRI contrast agent and to enhance the efficacy of cancer chemotherapy, herein for the first time we report a noncytotoxic asymmetrical cancer targeting polymer vesicle based on R-poly( l -glutamic acid)- block -poly(ε-caprolactone) [R is folic acid (FA) or DTPA]. Such asymmetrical vesicles have a cancer-targeting outer corona and a Gd(III)-chelating and drug-loading-enhancing inner corona, exhibiting an extremely high T 1 relaxivity (42.39 mM –1 s –1, 8-fold better than DTPA-Gd) and anticancer drug loading efficiency (52.6% for doxorubicin hydrochloride, DOX·HCl). Moreover, the DOX-loaded vesicles exhibited excellent antitumor activity (2-fold better than free DOX). This “chelating-just-inside” strategy for synthesizing asymmetrical polymer vesicles demonstrated promising potential theranostic applications in magnetic resonance imaging and cancer-targeted drug delivery.