Tumor microenvironment (TME) is the
survival environment for tumor
cells to proliferate and metastasize in deep tissue. TME contains
tumor cells, immune cells, stromal cells and a variety of active molecules
including reactive oxygen species (ROS). Inside the TME, ROS regulate
the oxidation–reduction (redox) homeostasis and promote oxidative
stress. Due to the rapid proliferation ability and specific metabolic
patterns of the TME, ROS pervade virtually all complex physiological
processes and play irreplaceable roles in protein modification, signal
transduction, metabolism, and energy production in various tumors.
Therefore, measurements of the dynamically, multicomponent simultaneous
changes of ROS in the TME are of great significance to reveal the
detailed proliferation and metastasis mechanisms of the tumor. Near-infrared
(NIR) and two-photon (TP) fluorescence imaging techniques possess
real-time, dynamic, highly sensitive, and highly signal-to-noise ratios
with deep tissue penetration abilities. With the rationally designed
probes, the NIR and TP fluorescence imaging techniques have been widely
used to reveal the mechanisms of how ROS regulates and constructs
complex signals and metabolic networks in TME. Therefore, we summarize
the design principles and performances of NIR and TP fluorescence
imaging of ROS in the TME in the last four years, as well as discuss
the advantages and potentials of these works. This Review can provide
guidance and prospects for future research work on TME and facilitate
the development of antitumor drugs.
Elevated nitric oxide (NO) within tumor-associated macrophages
(TAMs) suggests a reduction of TAM-mediated tumoral immune tolerance.
This cellular event could be a reliable indicator for efficacy evaluation
of antineoplastic drugs. However, a suitable method for TAM-specific
NO measurement is still lacking. In this work, a simple and fast efficacy
evaluation method for antineoplastic drugs is established based on
a ratiometric TAM-specific NO near-infrared (NIR) fluorescence probe
TAM-Cy-NO. Molecular fluorescence probe Cy-NO for NO response was
encapsulated in the TAM-targeting peptide (M2pep)-functionalized liposome
to construct TAM-Cy-NO. After TAM enters through M2pep, Cy-NO reacts
with NO specifically, resulting in a dose-dependent ratiometric fluorescence
signal (I
610/I
815) change manner. Utilizing this strategy, we observed that PLX-3397,
metformin, and ibrutinib triggered NO generation within TAM greater
than that with sorafenib. Notably, metformin and ibrutinib promoted
TNF-α and reduced PD-L1 expressions, which suggest reductions
of TAM-mediated immunosuppression. As expected, these drugs delayed
tumor progression in mice. This method provides a promising efficacy
evaluation strategy for rapid screening of antineoplastic drugs.
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