Rational Modulation Strategies to Improve Bioimaging Applications for Organic NIR‐II Fluorophores

Abstract

with optical simulation and empirical derivation is considered as "biologicalappropriate". [10,11] In addition, the autofluorescence intensity, effective attenuation coefficient, and scattering coefficient of biological components are significantly minimized in the NIR-II region (Figure 1). [12,13] Initially, Kevin Welsher et al. reported that the most prominent advantage of the reduced adverse factors is a deeper penetration depth beyond 1 µm by exploiting single-walled carbon nanotubes (SWNTs). [14] However, Smith et al. highlighted that the nonbiodegradable nature and needle-like structure of SWNTs can cause tissue damage and chronic toxicity. [12] Moreover, optical bioimaging in clinical applications employs small fluorescent molecules as imaging agents. [4] Consequently, current research progressively focuses on the relatively compact and minimally toxic nature of organic fluorophores that can be observed in NIR-II fluorescence imaging.Based on the development of organic NIR-II fluorophores, construction and modification are considered as two essential parts of interest. As diverse synthetic methods enable the combination of functional building blocks for facilitating NIR-II fluorescence, the modulation is vital for developing NIR-II fluorescence imaging. Although the biosafety of organic NIR-II fluorophores is a major concern, its advantages can be completely exploited based on its biocompatibility. [4,17,18] Therefore, the bioapplication of organic NIR-II fluorophores can be simultaneously enriched. An additional issue pertains to the unsatisfactory fluorescence quantum yield (QY) of organic NIR-II fluorophores. The simultaneous regulation of the ground and excited states promotes the easy-to-be-quenched property of organic NIR-II fluorophores, which adversely affects the fluorescence QY. [19,20] Moreover, the activatable properties exhibited by organic NIR-II fluorophores are related to modulation to induce a smarter signal output model rather than the "always ON" type.This study reviews the construction of organic NIR-II fluorophores in various molecular types (e.g., donor-acceptor (D-A) type, organic small molecules with π-conjugation systems, and organic polymers with π-conjugation systems). In addition, the modulation strategies for improving biosafety, fluorescence QY, biotargeting ability, and signal activatable features are summarized as well. Furthermore, this study highlights the current limitations that should be addressed in depth, including the future direction of the modulation strategy for the development of organic NIR-II fluorophores.The second near-infrared (NIR-II) window is highly effective in fluorescent bioimaging to obtain a deep view of living systems. Among numerous NIR-II fluorescent agents, organic fluorophores have been considered as ideal candidates in this field. Thus, modulation strategies should be considered to improve the performance and functionality of such agents. This review provides an overview of the development and construction of organic NIR-II fluorophores. More i...

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