Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
Angew Chem Int Ed Engl. 2018 Jun 11;57(24):7066-7070. doi: 10.1002/anie.201801984. Epub 2018 May 14.
Polymeric micelle-based drug delivery systems have dramatically improved the delivery of small molecular drugs, yet multiple challenges remain to be overcome. A polymeric nanomedicine has now been engineered that possesses an ultrahigh loading (59 %) of a glutathione (GSH)-sensitive heterodimeric multifunctional prodrug (HDMP) to effectively co-deliver two synergistic drugs to tumors. An HDMP comprising of chemotherapeutic camptothecin (CPT) and photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-α (HPPH) was conjugated via a GSH-cleavable linkage. The intrinsic fluorogenicity and label-free radio-chelation ( Cu) of HPPH enabled direct drug monitoring by fluorescence imaging and positron emission tomography (PET). Through quantitative PET imaging, HDMP significantly improves drug delivery to tumors. The high synergistic therapeutic efficacy of HDMP-loaded NPs highlights the rational design of HDMP, and presents exciting opportunities for polymer NP-based drug delivery.
基于聚合物胶束的药物传递系统极大地改善了小分子药物的传递，然而仍有许多挑战需要克服。现已设计出一种聚合物纳米药物，其具有超高载药量（59%）的谷胱甘肽（GSH）敏感的杂二聚体多功能前药（HDMP），可有效将两种协同药物递送至肿瘤。包含化疗药物喜树碱（CPT）和光敏剂 2-（1-己氧基乙基）-2-去乙烯基焦脱镁叶绿酸-α（HPPH）的 HDMP 通过 GSH 可裂解键连接。HPPH 的固有荧光性和无标记放射性螯合（ Cu）使荧光成像和正电子发射断层扫描（PET）能够直接进行药物监测。通过定量 PET 成像，HDMP 显著提高了药物向肿瘤的递送。载有 HDMP 的 NPs 的高协同治疗效果突出了 HDMP 的合理设计，并为基于聚合物 NP 的药物传递带来了令人兴奋的机会。
