Princess Margaret Cancer Centre, University Health Network, Canada.
Leslie Dan Faculty of Pharmacy, Department of Pharmaceutical Sciences, University of Toronto, Canada.
Angew Chem Int Ed Engl. 2016 May 17;55(21):6187-91. doi: 10.1002/anie.201600234. Epub 2016 Apr 13.
The discovery and synthesis of novel multifunctional organic building blocks for nanoparticles is challenging. Texaphyrin macrocycles are capable and multifunctional chelators. However, they remain elusive as building blocks for nanoparticles because of the difficulty associated with synthesis of texaphyrin constructs capable of self-assembly. A novel manganese (Mn)-texaphyrin-phospholipid building block is described, along with its one-pot synthesis and self-assembly into a Mn-nanotexaphyrin. This nanoparticle possesses strong resilience to manganese dissociation, structural stability, in vivo bio-safety, and structure-dependent T1 and T2 relaxivities. Magnetic resonance imaging (MRI) contrast enhanced visualization of lymphatic drainage is demonstrated with respect to proximal lymph nodes on the head and neck VX-2 tumors of a rabbit. Synthesis of 17 additional metallo-texaphyrin building blocks suggests that this novel one-pot synthetic procedure for nanotexaphyrins may lead to a wide range of applications in the field of nanomedicines.
新型多功能有机纳米粒子构建块的发现和合成具有挑战性。卟啉大环是多功能螯合剂。然而,由于难以合成能够自组装的卟啉结构,它们仍然难以作为纳米粒子的构建块。本文描述了一种新型锰(Mn)-卟啉-磷脂构建块,及其一锅法合成和自组装成 Mn-纳米卟啉。该纳米粒子具有很强的抗锰离解能力、结构稳定性、体内生物安全性以及结构依赖性 T1 和 T2 弛豫率。本文还证明了相对于头颈部 VX-2 肿瘤的近端淋巴结,该纳米粒子在淋巴引流的磁共振成像(MRI)对比增强可视化方面具有良好的效果。另外 17 种金属卟啉构建块的合成表明,这种新型的纳米卟啉一锅法合成程序可能会在纳米医学领域得到广泛应用。