Thermoactivatable polymer-grafted liposomes for low-invasive image-guided chemotherapy

Abstract

The objective of this study was to develop a thermotriggered, polymer-based liposomal drug carrier with an activatable magnetic resonance imaging (MRI) contrast property for monitoring the release of substances and for localized tumor therapy. The multimodal thermoactivatable polymer-grafted liposomes (MTPLs) were tested to investigate whether the accumulation of MTPLs in colon-26 grafted tumors could be visualized in vivo using MRI and optical imaging, whether MTPLs induce signal enhancement, reflecting the release of their contents, after triggering by short-term heating (42.5°C for 10 minutes) 9 hours after MTPL administration (late-phase triggering), and whether MTPLs can provide a sufficient antitumor effect. The imaging and therapeutic properties of MTPLs were tested both in vitro and in vivo (BALB/c nude mice: heated group with MTPLs (n = 5), nonheated group with MTPLs (n = 5), heated group with doxorubicin-free MTPLs (n = 5), nonheated group with manganese-free MTPLs (n = 5), and kinetics observation group (n = 3); N = 23). Through in vivo MRI and fluorescent imaging, the MTPLs were shown to have significantly accumulated in the grafted colon-26 tumors 8 hours after administration. Delayed thermotriggering (9 hours after administration) caused MR signal enhancement, reflecting the release of their contents, after a short exposure to tolerable heat. In addition, significant antitumor effects were observed after treatment. The proposed polymer-based activatable MTPLs with a "delayed thermotrigger" provide a promising technology for cancer theranostics that allows minimal adverse effects and rapid interactive therapy.