Finely Tailored Conjugated Small Molecular Nanoparticles for Near-Infrared Biomedical Applications

Near-infrared (NIR) phototheranostics (PTs) show higher tissue penetration depth, signal-to-noise ratio, and better biosafety than PTs in the ultraviolet and visible regions. However, their further advancement is severely hindered by poor performances and short-wavelength absorptions/emissions of PT agents. Among reported PT agents, conjugated small molecular nanoparticles (CSMNs) prepared from D-A-typed photoactive conjugated small molecules (CSMs) have greatly mediated this deadlock by their high photostability, distinct chemical structure, tunable absorption, intrinsic multifunctionality, and favorable biocompatibility, which endows CSMNs with more possibilities in biological applications. This review aims to introduce the recent progress of CSMNs for NIR imaging, therapy, and synergistic PTs with a comprehensive summary of their molecular structures, structure types, and optical properties. Moreover, the working principles of CSMNs are illustrated from photophysical and photochemical mechanisms and light-tissue interactions. In addition, molecular engineering and nanomodulation approaches of CSMs are discussed, with an emphasis on strategies for improving performances and extending absorption and emission wavelengths to the NIR range. Furthermore, the in vivo investigation of CSMNs is illustrated with solid examples from imaging in different scenarios, therapy in 2 modes, and synergistic PTs in combinational functionalities. This review concludes with a brief conclusion, current challenges, and future outlook of CSMNs.