Facile Synthesis of a Croconaine‐Based Nanoformulation for Optoacoustic Imaging and Photothermal Therapy

Abstract

Near‐infrared (NIR) light absorbing theranostic agents can integrate optoacoustic imaging and photothermal therapy for effective personalized precision medicine. However, most of these agents face the challenges of unstable optical properties, material‐associated toxicity, and nonbiodegradability, all of which limit their biomedical application. Several croconaine‐based organic agents able to overcome some of these limitations have been recently reported, but these suffer from complicated multistep synthesis protocols. Herein, the use of CR760, a croconaine dye with excellent optical properties, is reported for nanoparticle formulation and subsequent optoacoustic imaging and photothermal therapy. Importantly, CR760 can be conveniently prepared in a single step from commercially available materials. Furthermore, CR760 can be covalently attached, via a polyethylene glycol linker, to the αvβ3 integrin ligand c(RGDyC), resulting in self‐assembled nanoparticles (NPs) with cancer‐targeting capability. Such CR760RGD‐NPs exhibit strong NIR absorption, high photostability, high optoacoustic generation efficiency, and active tumor‐targeting, making them ideal candidates for optoacoustic imaging. Due to favorable electron transfer, CR760RGD‐NPs display a 45.37% photothermal conversion efficiency thereby rendering them additionally useful for photothermal therapy. Targeted tumor elimination, biosafety, and biocompatibility are demonstrated in a 4T1 murine breast tumor model. This work points to the use of CR760RGD‐NPs as a promising nanoagent for NIR‐based cancer phototheranostics.

Design Principles Governing the Development of Theranostic Anticancer Agents and Their Nanoformulations with Photoacoustic Properties

“…Liu et al [171] showcased the theranostic potential of PEGylated CR760-based dye nanoparticles (average diameter of ~23 nm) (Figure 16g). Their surface was also decorated with c(RGDyC) peptides for more effective targeting ability, which was validated by confocal imaging in vitro in 4T1 breast cancer cells.…”

Targeted contrast agents and activatable probes for photoacoustic imaging of cancer

“…112 Relative to antibody targeting, RGD-based peptides are readily accessible, exhibit low immunogenicity, and can be conveniently conjugated to various molecular structures via conventional conjugation chemistry. Although a vast number of RGD-based TCA for PA imaging have been developed, 20,113–143 we highlight several notable examples below.…”

Combined Photodynamic and Photothermal Therapy and Immunotherapy for Cancer Treatment: A Review

“… 119 In addition, Liu et al designed and synthesised nanoparticle CR760RGD by covalently linking saffron dye to αVβ3 integrin ligand C (RGDyC) through PEG, which showed strong NIR absorption and high photostability and active tumour targeting and can effectively eliminate tumors. 120 Notably, the synthesis of the above two nanoparticles overcomes past limitations, such as hypothermia, etc. However, more relevant studies are needed to further verify the applicability of its clinical PTT.…”