Mixed and Matched Metallo‐Nanotexaphyrin for Customizable Biomedical Imaging

Abstract

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 indium-manganese-nanotexaphyrin for dual modal single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). In vivo dual SPECT/MRI imaging of 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.

Stable J‐Aggregation of an aza‐BODIPY‐Lipid in a Liposome for Optical Cancer Imaging

“…In contrast, the porphysome is a recent example of a “one‐for‐all” approach in which the lipid nanoparticle is comprised of a single porphyrin‐lipid building block that when self‐assembled offers a multitude of intrinsic nanoscale functions . Previously developed porphyrin and porphyrin analog‐based lipids such as bacteriochlorophyll‐lipid and texaphyrin‐lipid have shown unique stimuli‐responsive properties and versatile metal‐chelation capabilities, respectively, for cancer imaging. We envision that it is possible for a non‐porphyrin‐based dye‐lipid building block, such as aza‐BODIPY, to assemble into a liposomal structure that introduces novel nanoscale optical properties and broadens the purview of “one‐for‐all” lipid nanoparticles.…”

Highly-Soluble Cyanine J-aggregates Entrapped by Liposomes for In Vivo Optical Imaging around 930 nm

“…However, the reason for the strong accumulation observed in the spleen (over 50 times more avidly than the liver on a per gram tissue basis) requires further investigation. Other types of PEGylated nanoparticles have been previously observed to accumulate substantially more in the spleen than liver 44, 45. Of note, Cui and colleagues found that large PEG nanoparticles of both 500 nm and 280 nm accumulated strongly in the spleen, compared to liver.…”

Porphyrin-Based Nanomedicines for Cancer Treatment

“…Porphyrin molecules smartly revitalized the liposomes with excellent therapeutic efficacy and myriad of extensibilities. The porphysome was a fascinating, multifunctional theranostic regime for cancer treatments; Zheng and co-workers have successfully implemented them into various kinds of tumor models for phototherapies (photodynamic and photothermal therapy), ,,− NIRFI, ,− MRI, ,, PAI, ,, SPECT, and PET. ,, …”