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.

The size and morphology of metals determine their plasmon resonances. How to elegantly tune their architectures to obtain optical properties as required (e.g., strong absorption in the near-infrared (NIR) wavelengths) is a bottleneck for phototherapy. Inspired by biomineralization, we develop a simple but robust strategy to fabricate silver nanocages (Ag NCs) based on peptide-directed mineralization of silver. The Ag NCs are organic–inorganic hybrids with octreotide (OCT) templated decoration of Ag shells that are composed of Ag NPs. This hierarchical organization makes Ag NPs get together in close proximity, which facilitates ultrastrong plasmonic coupling to shift the resonant excitation from the visible (420 nm) to the NIR region (810 nm). In addition, the surface plasmon resonance peak of the Ag NCs in the NIR region can be subtly tuned by varying the volume of added silver nitrate (AgNO3) to control the size and morphology of mineralized Ag NCs. The Ag NCs have a light-to-heat conversion efficiency of 46.1%, which is to our knowledge the highest among Ag-based photothermal agents (PTAs). The Ag NCs can selectively induce death of cancer cells in vitro under NIR irradiation at 808 nm and show improved cytocompatibility for normal cells relative to pure Ag NPs. Following intratumor injection into uterine cervix cancer cells (U14) tumor-bearing mice, Ag NCs exert remarkable antitumor performance with tumor killing efficacy up to 82.7% and good biocompatibility in photothermal therapy, suggesting their potential application to work as photothermal nanomedicine for cancer therapy.

We developed a mitochondria-targeted near-infrared activatable fluorescent/photoacoustic (NIR FL/PA) probe for the selective detection of prostate cancer-derived ALP and aggregation-enhanced photothermal therapy.