Molecular Engineered Squaraine Nanoprobe for NIR-II/Photoacoustic Imaging and Photothermal Therapy of Metastatic Breast Cancer

Abstract

Various squaraine dyes have been developed for biological imaging. Nevertheless, squaraine dyes with emission in the second window (NIR-II, 1000–1700 nm) have few reports largely due to the short of a simple and universal design strategy. In this contribution, molecular engineering strategy is explored to develop squaraine dyes with NIR-II emission. First, NIR-I squaraine dye SQ2 is constructed by the ethyl-grafted 1,8-naphtholactam as donor units and square acid as acceptor unit in a donor–acceptor–donor (D–A–D) structure. To red-shift the fluorescence emission into NIR-II window, malonitrile, as a forceful electron-withdrawing group, is introduced to strengthen square acid acceptor. As a result, the fluorescence spectrum of acceptor-engineered squaraine dye SQ1 exhibits a significant red-shift into NIR-II window. To translate NIR-II fluorophores SQ1 into effective theranostic agents, fibronectin-targeting SQ1 nanoprobe was constructed and showed excellent NIR-II imaging performance in angiography and tumor imaging, including lung metastatic foci in deep tissue. Furthermore, SQ1 nanoprobe can be used for photoacoustic imaging and photothermal ablation of tumors. This research demonstrates that the donor–acceptor engineering strategy is feasible and effective to develop NIR-II squaraine dyes.

Squaraine Dyes for Photovoltaic and Biomedical Applications

“…Reproduced with permission. [ 135 ] Copyright 2020, American Chemical Society. h) UV–vis–NIR absorption spectra of the SQP‐NPs (J) and SQP‐NPs (H).…”

“…Figure 25a shows a scheme of photothermal therapy, in which SQ1 was injected to the tumor cell in form of nanoprobe and then generated heat when exposed to NIR light. [ 135 ] Energy gap from intramolecular charge transfer between HOMO and LUMO can lead to long‐wavelength absorption (Figure 25b). Excited molecules release heat to be stabilized and thus become heat source.…”

Recent advances in applications of multimodal ultrasound-guided photoacoustic imaging technology

“…Hyperpyrexia refers to the rise of tissue temperature to 42-46°C, while irreversible PTA can lead to tissue necrosis, which is equivalent to 240 min at 43°C or 1 s at 54°C. Yao et al [26] reported leveraging Moreover, a SQ1 nanoprobe can be used for PTA of tumors. Depending on the photothermal effect of the SQ1 nanoprobe, PAI can be carried out simultaneously (Fig.…”

“…PAI of fibronectin-positive MDAMB-231 tumors at 0, 1, 2, 6, 12 and 24 h postinjection of SQ1 nanoprobe or SQ1@DSPE (control) i.v[26].…”

<p>Facile Synthesis of Melanin-Dye Nanoagent for NIR-II Fluorescence/Photoacoustic Imaging-Guided Photothermal Therapy</p>

“…2 Recent studies, including those regarding the detection of metastatic lymph nodes, 3 tumor and vessel imaging, [4][5][6] and intraoperative guidance, 7,8 have shown that biological imaging advantages significantly improves as wavelengths increase. Thus far, quantum dots, [9][10][11] carbon nanotubes, 12,13 rare earth-doped nanoparticles, 14,15 squaraine dyes, 16,17 semiconducting polymer nanoparticles, 18 and small-molecule dyes 5,19,20 have all been actively used for NIR-II imaging. The recent rapid development of small molecule dyes, in particular, has led to the use of effective probes for NIR-II fluorescence bioimaging.…”