Intrabilayer (64)Cu Labeling of Photoactivatable, Doxorubicin-Loaded Stealth Liposomes.
Intrabilayer (64)Cu Labeling of Photoactivatable, Doxorubicin-Loaded Stealth Liposomes.
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光活化、负载阿霉素的隐形脂质体的双层内 Cu-64 标记
DOI：
10.1021/acsnano.7b06578
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发表时间：
2017-12-26
期刊：
影响因子：
17.1
通讯作者：
Lovell JF
中科院分区：
文献类型：
--
作者：
Luo D;Goel S;Liu HJ;Carter KA;Jiang D;Geng J;Kutyreff CJ;Engle JW;Huang WC;Shao S;Fang C;Cai W;Lovell JF
装载阿霉素（Dox）的隐形脂质体（类似于临床使用的脂质体）可以掺入少量的卟啉磷脂（PoP），以实现化学光疗（CPT）。PoP也是一种内在的和双层内的64 Cu螯合剂，尽管放射性标记如何影响药物递送尚未被评估。在这里，我们表明64 Cu可以放射性标记预先形成的负载Dox的PoP脂质体（包含1%乙醇）的稳定双层，而不会诱导药物泄漏。双层内铜标记的Dox-PoP脂质体在体外和体内的物理参数、药代动力学和CPT疗效方面与未标记的脂质体几乎相同。正电子发射断层扫描和近红外荧光成像可视化原位乳腺肿瘤的小鼠与被动脂质体积累后管理。用665 nm光（200 J/cm 2）的单次CPT治疗强烈抑制原发性肿瘤生长。基于NIR成像，脂质体在肺转移瘤中积聚。这些结果确立了通过装载Dox的隐形PoP脂质体的固有多模态成像指导CPT干预的可行性。
Doxorubicin (Dox)-loaded stealth liposomes (similar to those in clinical use) can incorporate small amounts of porphyrin–phospholipid (PoP) to enable chemophototherapy (CPT). PoP is also an intrinsic and intrabilayer 64Cu chelator, although how radiolabeling impacts drug delivery has not yet been assessed. Here, we show that 64Cu can radiolabel the stable bilayer of preformed Dox-loaded PoP liposomes with inclusion of 1% ethanol without inducing drug leakage. Dox-PoP liposomes labeled with intrabilayer copper behaved nearly identically to unlabeled ones in vitro and in vivo with respect to physical parameters, pharmacokinetics, and CPT efficacy. Positron emission tomography and near-infrared fluorescence imaging visualized orthotopic mammary tumors in mice with passive liposome accumulation following administration. A single CPT treatment with 665 nm light (200 J/cm2) strongly inhibited primary tumor growth. Liposomes accumulated in lung metastases, based on NIR imaging. These results establish the feasibility of CPT interventions guided by intrinsic multimodal imaging of Dox-loaded stealth PoP liposomes.
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