National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China.
Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Adv Mater. 2018 Mar;30(13):e1704934. doi: 10.1002/adma.201704934. Epub 2018 Feb 12.
Nanoengineering of cell membranes holds great potential to revolutionize tumor-targeted theranostics, owing to their innate biocompatibility and ability to escape from the immune and reticuloendothelial systems. However, tailoring and integrating cell membranes with drug and imaging agents into one versatile nanoparticle are still challenging. Here, multicompartment membrane-derived liposomes (MCLs) are developed by reassembling cancer cell membranes with Tween-80, and are used to conjugate Zr via deferoxamine chelator and load tetrakis(4-carboxyphenyl) porphyrin for in vivo noninvasive quantitative tracing by positron emission tomography imaging and photodynamic therapy (PDT), respectively. Radiolabeled constructs, Zr-Df-MCLs, demonstrate excellent radiochemical stability in vivo, target 4T1 tumors by the enhanced permeability and retention effect, and are retained long-term for efficient and effective PDT while clearing gradually from the reticuloendothelial system via hepatobiliary excretion. Toxicity evaluation confirms that the MCLs do not impose acute or chronic toxicity in intravenously injected mice. Additionally, Zr-labeled MCLs can execute rapid and highly sensitive lymph node mapping, even for deep-seated sentinel lymph nodes. The as-developed cell membrane reassembling route to MCLs could be extended to other cell types, providing a versatile platform for disease theranostics by facilely and efficiently integrating various multifunctional agents.
细胞膜的纳米工程具有彻底改变肿瘤靶向治疗的巨大潜力，这要归功于它们固有的生物相容性以及逃避免疫和网状内皮系统的能力。然而，将细胞膜与药物和成像剂定制并整合到一个多功能纳米颗粒中仍然具有挑战性。在这里，通过重新组装含有 Tween-80 的癌细胞膜来开发多隔室膜衍生的脂质体 (MCL)，并通过去铁胺螯合剂将 Zr 与 MCL 结合，并负载四(4-羧基苯基)卟啉，用于通过正电子发射断层扫描成像进行体内非侵入性定量追踪，以及光动力疗法 (PDT)。放射性标记的构建体，Zr-Df-MCL，在体内表现出优异的放射化学稳定性，通过增强的通透性和保留效应靶向 4T1 肿瘤，并通过肝胆排泄逐渐从网状内皮系统清除，从而实现高效和有效的 PDT。毒性评估证实 MCL 对静脉注射的小鼠没有急性或慢性毒性。此外，Zr 标记的 MCL 可以快速且高度敏感地进行淋巴结成像，甚至可以对深部前哨淋巴结进行成像。通过这种细胞膜重组方法制备 MCL 可以扩展到其他细胞类型，通过简便高效地整合各种多功能药物，为疾病治疗提供了一个通用的平台。
