Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

Abstract

Near-infrared fluorescence (NIRF) imaging is an attractive modality for early cancer detection with high sensitivity and multi-detection capability. Due to convenient modification by conjugating with moieties of interests, NIRF probes are ideal candidates for cancer targeted imaging. Additionally, the combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Moreover, nanoparticles loaded with NIRF dyes and anticancer agents contribute to the synergistic management of cancer, which integrates the advantage of imaging and therapeutic functions to achieve the ultimate goal of simultaneous diagnosis and treatment. Appropriate probe design with targeting moieties can retain the original properties of NIRF and pharmacokinetics. In recent years, great efforts have been made to develop new NIRF probes with better photostability and strong fluorescence emission, leading to the discovery of numerous novel NIRF probes with fine photophysical properties. Some of these probes exhibit tumoricidal activities upon light radiation, which holds great promise in photothermal therapy, photodynamic therapy, and photoimmunotherapy. This review aims to provide a timely and concise update on emerging NIRF dyes and multifunctional agents. Their potential uses as agents for cancer specific imaging, lymph node mapping, and therapeutics are included. Recent advances of NIRF dyes in clinical use are also summarized.

Keywords: cancer targeting; cancer therapy; imaging; nanoparticles; near infrared dyes.

Figure 1

Basic chemical structures of NIRF dyes. Abbreviations: NIRF, near infrared fluorescent; BODIPY, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene.

Figure 2

Structural characteristics of nanoparticle-based NIRF probes. Notes: QDs are comprised of a core/shell structure and a coating that minimizes their potential toxicity. Furthermore, specific moieties with targeting ability can be linked to the surface. Nonmetallic nanoparticles include dye-loaded micelles and polymer-based structures that retain NIRF dyes inside or on the surface. Nanorods, nanodots, nanoclusters, and nanotubes are mainly developed using gold nanomaterials. Most of the targeted dyes are linked with moieties that have selective binding activity. Activatable NIRF dyes originally have little fluorescence emission; when disintegrated, these dyes emit strong fluorescence. Abbreviations: NIRF, near infrared fluorescent; QDs, quantum dots.

Figure 3

NIRF cancer imaging using IR783 (0.375 mg/kg) in athymic nude mice with subcutaneous prostate cancer. Abbreviation: min, minimum; max, maximum; NIRF, near infrared fluorescent.

Figure 4

Schematic illustration of PTT and PDT. Notes: NIRF probes were incubated with cancer cells. Upon light radiation, the accumulation of NIRF probes drastically increased the efficiency of PTT through effective conversion of light energy into heat, resulting in laser-induced thermal damage to cancer cells. In PDT settings, NIRF probes facilitate the generation of cytotoxicity-free radicals as singlet oxygens, and initiate an inflammatory microenvironment that leads to cancer cell death after light radiation. Abbreviations: NIRF, near infrared fluorescent; PDT, photodynamic therapy; PTT, photothermal therapy.