Mixed and Matched Metallo‐Nanotexaphyrin for Customizable Biomedical Imaging

: The discovery and synthesis of multifunctional organic building blocks for nanoparticles have remained challenging. Texaphyrin macrocycles are multifunctional, all-organic compounds that possess versatile metal-chelation capabilities and unique theranostics properties for biomedical applications. Unfortunately, there are significant difficulties associated with the synthesis of texaphyrin-based subunits capable of forming nanoparticles. Herein, the detailed synthesis of a texaphyrin-phospholipid building block is reported via a key 1,2-dinitrophenyl-phospholipid intermediate, along with stable chelation of two clinically relevant metal ions into texaphyrin-lipid without compromising their self-assembly into texaphyrin nanoparticles or nanotexaphyrin. A postinsertion methodology to quantitatively insert a variety of metal-ions into preformed nanotexaphyrins is developed and employed to synthesize a structurally stable, mixed 111 indium-manganese-nanotexaphyrin for dual modal single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). In vivo dual SPECT/MRI imaging of 111 In-Mn-nanotexaphyrins in an orthotopic prostatic PC3 mouse model demonstrates complementary signal enhancement in the tumor with both modalities at 22 h post intravenous administration. This result highlights the utility of hybrid metallo-nanotexaphyrins to achieve sensitive and accurate detection of tumors by accommodating multiple imaging modalities. The power of this mixed and matched metallo-nanotexaphyrin strategy can be unleashed to allow a diverse range of multifunctional biomedical imaging.