Original Article| Volume 166, ISSUE 6, P660-673.e1, December 2015

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

Published:August 05, 2015DOI:
      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.


      2D (two-dimensional), DDS (drug delivery system), DPPC (dipalmitoylphosphatidylcholine), EPR (enhanced permeability and retention), FOV (field of view), MBE (manganese-bound relaxivity enhancement), Mn (manganese), MnSO4 (manganese sulfate), MRI (magnetic resonance imaging), MTPL (multimodal thermoactivatable polymer-grafted liposome), NA (number of acquisitions), PEG (polyethylene glycol), R1 (longitudinal relaxation rate), R2 (transverse relaxation rate), ST (slice thickness), T1 (longitudinal relaxation time), T2 (transverse relaxation time), TR (repetition time), TE (echo time), TPL (thermosensitive polymer-grafted liposome), TSL (temperature-sensitive liposomes)
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