Department of Biomedical Engineering, University at Buffalo, State University of New York , Buffalo, New York 14260, United States.
Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM) , 280 South Chongqing Road, Shanghai 200025, China.
ACS Nano. 2017 Dec 26;11(12):12482-12491. doi: 10.1021/acsnano.7b06578. Epub 2017 Dec 5.
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 Cu chelator, although how radiolabeling impacts drug delivery has not yet been assessed. Here, we show that Cu 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/cm) 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.
阿霉素（Dox）负载的隐形脂质体（类似于临床使用的脂质体）可以掺入少量卟啉磷脂（PoP）以实现化学光疗（CPT）。PoP 也是内在的双分子层 Cu 螯合剂，尽管放射性标记如何影响药物递送尚未得到评估。在这里，我们表明，Cu 可以用 1%乙醇对预先形成的负载 Dox 的 PoP 脂质体的稳定双层进行放射性标记，而不会引起药物泄漏。用内双层铜标记的 Dox-PoP 脂质体在体外和体内与未标记的脂质体在物理参数、药代动力学和 CPT 效果方面几乎相同。正电子发射断层扫描和近红外荧光成像在给予后通过被动脂质体积累可视化了小鼠的原位乳腺肿瘤。单次 CPT 治疗（665nm 光，200J/cm）强烈抑制了原发性肿瘤的生长。基于近红外成像，脂质体在肺转移部位聚集。这些结果确立了通过负载 Dox 的隐形 PoP 脂质体的内在多模式成像指导 CPT 干预的可行性。
