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Mao et al. Chem Synth 2023;3:26 https://dx.doi.org/10.20517/cs.2022.41 Page 17 of 33

It is expected that the FLI in the visible spectroscopy and the NIR-I windows has some limitations and
disadvantages [128-130] , such as insufficient spatial resolution and penetration and a lack of anatomical structure
information. This is due to the mutual effects between light and living tissues, which can cause rigorous
autofluorescence, scattering, and absorption . To overcome these problems, the range of FLI has been
[131]
broadened to the NIR-II region .
[125]
Photoacoustic imaging
The material must have a strong photothermal conversion efficiency to be used in photoacoustic imaging
(PAI). Because of their strong absorption of copper chalcogenides in the near-infrared region (700-1,500
nm), they have become the preferred choice for photothermal conversion agents . The use of copper-
[132]
based chalcogenides as photothermal reagents was first reported by Li et al. in 2000, who synthesized -SH-
coated copper sulfide nanoparticles . According to the existing reports, some copper chalcogenides X Y
[133]
2
(X = Cu/Ag/Au, Y = S/Se/Te) were worthy of consideration because of their easy molecular formula,
complicated crystal texture, and fickle composition, which provide inconceivably rich properties for a
variety of applications of thermal conversion. Their characteristics in PAI and PTT have been owing to the
strong LSPR absorption in the NIR window generated from copper deficiency . Zhang et al. reported a
[134]
novel application of ultra-small cuprous selenide as a photothermal therapeutic agent for multimodal
imaging , which is shown in Figure 11A and B. It demonstrated the synthesis process of the material and
[135]
its imaging and therapeutic applications in vivo. The Cu Se had long circulation times in the blood and can
2-x
accumulate at tumor sites through the enhanced permeability and retention effect. In addition, they can be
labeled with nuclides ( Tc) for SPECT imaging to reveal tumor foci. Bao et al. developed a nanocomplex
99m
by modifying PD1 with gold nanoparticles on the surface of Cu Se (GPSeCS@PD-1) and applied it to
2-x
imaging and treating tumor-bearing mice. The PAI and PTT images in Figure 11C and D showed an
obvious contrast between the PAI signal and the high temperature of 53.4 C. This temperature caused the
o
cancer cells to heat up and necrosis of cancer cells. PTT treatment has obvious inhibition and ablation
effect. Bao et al. and other contributors have used synthetic copper for PAI and PTT . The synthetic
[136]
copper was widely used for PAI and PTT by Chen et al. and other contributors [74,138,139] .
[137]
Diagnosis and therapy of cancer
Cancer has become a significant threat to our well-being and health in modern society . Currently,
[140]
surgery, chemotherapy, and radiotherapy remain the primary strategies for cancer therapy. However,
limited by indication, contraindication, and side effects of operation, chemotherapy and radiotherapy are
usually reserved for patients with moderate or advanced cancer. To a certain extent, these treatments can
cause additional pain and other toxic side effects for patients. In the field of senior nanoscience, single
nanoparticles could afford diverse methods for diagnosis and therapy . They are utilized by their physical
[74]
and chemical properties of the nano-agents or through surface modification loading with different kinds of
imaging and therapeutic agents . Due to the enhanced permeability and retention [142,143] effect, they can be
[141]
engineered to respond to precise stimuli, providing physicians with diagnostic and treatment response
information. Endogenous stimuli, such as pH changes , hypoxia, and enzymes present in the tumor
[144]
microenvironment (TME) [144-147] , as the same as visually applied exogenous stimuli, including light ,
[145]
temperature, ultrasound, and magnetic field, are essential for the early cancer diagnosis and therapy.

An earlier diagnosis is essential for better medical outcomes and higher 5-year survival rates. Thus, one of
the key-knob to precise cancer treatment is how to understand the targeting procedure. Up to now, there
are several strategies to improve the NPs based targeting efficiency. For example, one common approach is
to combine nanoparticles with folic acid (FA) , targeting peptides or antibodies to achieve receptor-
[130]
[147]
[144]
mediated endocytosis, which has an instant effect on the enhancement of diagnostic value toward a wide
diversity of cancers.