Bioinspired nanoparticles for near infrared biomedical imaging

Abstract

The visualization and detection of deeply buried biological features at cellular size remains a major clinical challenge in disease diagnosis. In this regard, molecular imaging represents the upcoming advancement in biomedicine as it enables real-time visualization and characterization of physiological processes at both cellular and molecular levels. Unfortunately, the conventional imaging modalities routinely used in clinics, such as ultrasound, X-ray computed tomography, magnetic resonance imaging, etc., fail to address the aforementioned challenges. Despite offering a high penetration depth throughout the tissue, these techniques have a low spatial resolution, especially in soft tissue. As a result, identifying small tumor masses developed at the initial stage of cancer remains below their threshold value. On the other hand, the optical imaging techniques offer a high spatial resolution, enables visualization of the biological processes at the subcellular level; though, they are not suited for deep-tissue penetration. Nonetheless, the optical imaging in the near-infrared (NIR) region promises high spatial resolution and deeper penetration depth due to low endogenous absorption, low photon scattering, and negligible autofluorescence from the surrounding tissue. Therefore, NIR fluorescence imaging enabling high spatial resolution is advantageous for early-stage disease diagnosis and other biomedical applications. In this direction, several NIR active exogenous contrast agents such as quantum dots, carbon nanotubes, semiconducting polymers, and small-molecule organic dyes have been developed during the last few years. However, the applications of these exogenous contrast agents in optical imaging are limited due to their cytotoxicity and other unfavorable attributes. Therefore, using a biocompatible NIR active contrast agent for optical imaging is crucial for disease diagnosis and treatment. Indocyanine green (ICG) is the United States Food and Drug Administration (FDA) approved NIR active dye used in clinics for the last 60 years. The ICG facilitates deep tissue optical visualization as it has excitation and emission wavelengths in the NIR range (780/810 nm), as shown in Fig. a. Despite having suitable optical properties, free ICG has not been used to the fullest for biomedical applications due to its poor optical stability, concentration-dependent aggregation, photo- and thermal degradation and short circulation time in the body. These limitations of ICG could be overcome by encapsulating it within the nanoparticles (NPs), which will enhance its optical stability. Therefore, the development of an efficient nanocarrier is an utmost need for the site-specific delivery of an optically active form of ICG.