Protein & Peptide Pharmaceutical Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
J Control Release. 2013 Oct 28;171(2):133-42. doi: 10.1016/j.jconrel.2013.07.005. Epub 2013 Jul 14.
Polymeric micelles have been proven to be a promising nano-sized system for drug delivery. Understanding its in vivo behaviors at the whole body, tissue and cellular levels is critical for translating this drug delivery system into clinical practice. In this study, the 14.5 nm micelles made of polyethylene glycol-phosphatidylethanolamine (PEG-PE) for delivery of doxorubicin and vinorelbine were investigated. Using confocal and two-photon microscopy imaging of live mice or tissue sections, we observed that after systemic administration, the fluorescently labeled PEG-PE micelles encapsulating doxorubicin migrated through blood vessels in entirety into the interstitial tissue, collected by lymphatic vessels, and accumulated in lymph nodes. Importantly, encapsulated drugs such as vinorelbine (Nanovin), preferentially accumulate in lymph nodes when compared to the free drugs. Moreover, the in vivo bioluminescent imaging showed that Nanovin significantly reduced lymph node metastasis rate (P<0.05) in 4 T1-luc2 murine breast tumor bearing mice. Finally, we observed that Nanovin enhanced antitumor activity against primary tumors and lung metastases while having low toxicity in various 4 T1 tumor models. This study suggests that PEG-PE micelle is a promising drug delivery system for the treatment of lymphatic metastases, and may also have important applications in other lymphatic system-related diseases.
聚合物胶束已被证明是一种很有前途的药物传递的纳米级系统。了解其在全身、组织和细胞水平的体内行为对于将这种药物传递系统转化为临床实践至关重要。在这项研究中，研究了由聚乙二醇-磷脂酰乙醇胺（PEG-PE）制成的 14.5nm 胶束，用于递送阿霉素和长春瑞滨。通过对活小鼠或组织切片进行共聚焦和双光子显微镜成像，我们观察到，在全身给药后，荧光标记的阿霉素包封的 PEG-PE 胶束完整地穿过血管进入间质组织，被淋巴管收集，并在淋巴结中积累。重要的是，与游离药物相比，包封的药物（如长春瑞滨（Nanovin））优先在淋巴结中积累。此外，体内生物发光成像显示，Nanovin 显著降低了 4T1-luc2 荷瘤小鼠的淋巴结转移率（P<0.05）。最后，我们观察到 Nanovin 增强了对原发性肿瘤和肺转移的抗肿瘤活性，同时在各种 4T1 肿瘤模型中具有低毒性。这项研究表明，PEG-PE 胶束是一种很有前途的用于治疗淋巴转移的药物传递系统，并且在其他与淋巴系统相关的疾病中也可能有重要的应用。
