Journal Article Thermoactivatable Polymer-grafted Liposomes for Low-invasive Image-guided Chemotherapy

Aoki, Ichio  ,  Yoneyama, Misao  ,  Hirose, Jun  ,  Minemoto, Yuzuru  ,  Koyama, Takayoshi  ,  Kokuryo, Daisuke  ,  Murayama, Shuhei  ,  Bakalova, Rumiana  ,  Saga, Tusneo  ,  Aoshima, Sadahito  ,  Kono, Kenji  ,  Ishizaka, Yukihito

166 ( 6 )  , pp.660 - 673 , 2015-08 , Elsevier
The objective of this study was to develop a thermo-triggered, polymer-based liposomal drug carrier with an activatable MRI contrast property for monitoring the release of substances and for localized tumor therapy. The multimodal thermo-activatable polymer-grafted liposomes (MTPLs) was tested 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 contents-release after triggering by tolerable short-term heating (42.5°C for 10 min) 8 h after MTPL administration (late-phase triggering), and whether MTPLs can provide a sufficient anti-tumor 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), non-heated group with MTPLs (n = 5), heated group with doxorubicin-free MTPLs (n = 5), non-heated 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 h after administration. Delayed thermo-triggering (9 h after administration) caused MR signal enhancement reflecting the contents-release upon short exposure to tolerable heat. In addition, significant anti-tumor effects were observed after treatment. The proposed polymer-based activatable MTPLs with a ‘delayed thermo-trigger’ provide a promising technology for cancer theranostics that allows for minimal side effects and rapid interactive therapy.

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