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

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• 作者：Ichio Aoki^a ; ^{aoki@nirs.go.jp" class="auth_mail" title="E-mail the corresponding author} ; Misao Yoneyama^a ; Jun Hirose^b ; Yuzuru Minemoto^c ; Takayoshi Koyama^c ; Daisuke Kokuryo^a ; Rumiana Bakalova^a ; Shuhei Murayama^a ; Tsuneo Saga^a ; Sadahito Aoshima^d ; Yukihito Ishizaka^c ; Kenji Kono^b
• 关键词：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 tim
• 刊名：Translational Research
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：166
• 期：6
• 页码：660-673.e1
• 全文大小：2027 K

文摘

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.