Near Infrared Fluorescence Imaging in Nano-Therapeutics and Photo-Thermal Evaluation

Abstract

The unresolved and paramount challenge in bio-imaging and targeted therapy is to clearly define and demarcate the physical margins of tumor tissue. The ability to outline the healthy vital tissues to be carefully navigated with transection while an intraoperative surgery procedure is performed sets up a necessary and under-researched goal. To achieve the aforementioned objectives, there is a need to optimize design considerations in order to not only obtain an effective imaging agent but to also achieve attributes like favorable water solubility, biocompatibility, high molecular brightness, and a tissue specific targeting approach. The emergence of near infra-red fluorescence (NIRF) light for tissue scale imaging owes to the provision of highly specific images of the target organ. The special characteristics of near infra-red window such as minimal auto-fluorescence, low light scattering, and absorption of biomolecules in tissue converge to form an attractive modality for cancer imaging. Imparting molecular fluorescence as an exogenous contrast agent is the most beneficial attribute of NIRF light as a clinical imaging technology. Additionally, many such agents also display therapeutic potentials as photo-thermal agents, thus meeting the dual purpose of imaging and therapy. Here, we primarily discuss molecular imaging and therapeutic potentials of two such classes of materials, i.e., inorganic NIR dyes and metallic gold nanoparticle based materials.

Keywords: NIR fluorescence; cancer; gold nanoparticle; molecular imaging; photothermal therapy.

Figure 1

Schematic illustrating biological effects linked to stage-wise thermal increments with corresponding temperature rise.

Figure 2

Preclinical test results showing ex vivo and in vivo imaging and photothermal effect measurement of indocyanine green (ICG)-micelle with or without doxorubicin (DOX) drug loaded nanoparticles. (A) Ex vivo imaging of ICG from free ICG/DOX and ICG/DOX-micelles in heart, liver, spleen, lung, kidney, and tumor of the mice at 24 h post-injection at the dose of 7.5 mg/kg ICG/DOX, respectively; (B) In vivo near-infrared fluorescence (NIRF) imaging of the mice bearing A549 tumor injected with I/D-micelles at the dose of 7.5 mg/kg ICG/DOX at 1, 2, 4, and 6 days post-injection, respectively; (C) Tumor growth inhibition profiles of the mice bearing A549 tumor injected with various formulations; (D) Photographic view of tumors extracted from the mice bearing A549 tumor at the end of the experiment. Figure adapted from [25].

Figure 3

Schematic showing gold nanoparticle based near infra-red (NIR) mediated image guided photo-thermal therapy. EPR, enhanced permeability and retention effect.

Figure 4

2D vs. 3D imaging of NIRF probe in mouse xenograft. (A) 2D planer image showing NIRF signal at source (tumor); (B) 3D coronal, sagittal, and transaxial image views with slice plane optimization, showing the center of mass of the tumor from the surface of the body; (C) Corresponding coronal, sagittal, and transaxial image views with the 3D region of interest (ROI) marked on reconstructed mouse image with overlapping organ atlas.