Structure-Inherent Tumor-Targeted IR-783 for Near-Infrared Fluorescence-Guided Photothermal Therapy.

IR-783, a commercially available near-infrared (NIR) heptamethine cyanine dye, has been used for selective tumor imaging in breast, prostate, cervical, and brain cancers in vitro and in vivo. Although the molecular mechanism behind the structure-inherent tumor targeting of IR-783 has not been well-demonstrated, IR-783 has unique properties such as a good water solubility and low cytotoxicity compared with other commercial heptamethine cyanine dyes. The goal of this study is to evaluate the phototherapeutic efficacy of IR-783 as a tumor-targeted photothermal agent in human colorectal cancer xenografts. The results demonstrate that IR-783 shows both the subcellular localization in HT-29 cancer cells and preferential accumulation in HT-29 xenografted tumors 24 h after its intravenous administration. Furthermore, the IR-783 dye reveals the superior capability to convert NIR light into heat energy under 808 nm NIR laser irradiation in vitro and in vivo, thereby inducing cancer cell death. Taken together, these findings suggest that water-soluble anionic IR-783 can be used as a bifunctional phototherapeutic agent for the targeted imaging and photothermal therapy (PTT) of colorectal cancer. Therefore, this work provides a simple and effective approach to develop biocompatible, hydrophilic, and tumor-targetable PTT agents for targeted cancer phototherapy.

Tumor-Targeted Squaraine Dye for Near-Infrared Fluorescence-Guided Photodynamic Therapy.

Many efforts have been made to develop near-infrared (NIR) fluorescent dyes with high efficiency for the NIR laser-induced phototherapy of cancer. However, the low tumor targetability and high nonspecific tissue uptake of NIR dyes in vivo limit their applications in preclinical cancer imaging and therapy. Among the various NIR dyes, squaraine (SQ) dyes are widely used due to their high molar extinction coefficient, intense fluorescence, and excellent photostability. Previously, benzoindole-derived SQ (BSQ) was prepared by incorporating carboxypentyl benzoindolium end groups into a classical SQ backbone, followed by conjugating with cyclic RGD peptides for tumor-targeted imaging. In this study, we demonstrate that the structure-inherent tumor-targeting BSQ not only shows a high fluorescence quantum yield in serum but also exhibits superior reactive oxygen species (ROS) generation capability under the 671 nm laser irradiation for effective photodynamic therapy (PDT) in vitro and in vivo. Without targeting ligands, the BSQ was preferentially accumulated in tumor tissue 24 h post-injection, which was the optimal timing of the laser irradiation to induce increments of ROS production. Therefore, this work provides a promising strategy for the development of photodynamic therapeutic SQ dyes for targeted cancer therapy.

Rational Design of a Small Molecular Near-Infrared Fluorophore for Improved In Vivo Fluorescence Imaging.

The near-infrared (NIR) fluorescence imaging modality has great potential for application in biomedical imaging research owing to its unique characteristics, such as low tissue autofluorescence and noninvasive visualization with high spatial resolution. Although a variety of NIR fluorophores are continuously reported, the commercially available NIR fluorophores are still limited, owing to complex synthetic processes and poor physicochemical properties. To address this issue, a small molecular NIR fluorophore (SMF800) was designed and developed in the present work to improve in vivo target-specific fluorescence imaging. After conjugation with pamidronate (PAM) and bovine serum albumin (BSA), the SMF800 conjugates exhibited successful in vivo targeting in bone and tumor tissues with low background uptake, respectively. The improved in vivo performance of the SMF800 conjugate demonstrated that the small molecular NIR fluorophore SMF800 can be widely used in a much broader range of imaging applications. The structure of SMF800, which was developed by considering two important physicochemical properties, water solubility and conjugatability, is first introduced. Therefore, this work suggests a simple and rational approach to design small, hydrophilic, and conjugatable NIR fluorophores for targeted bioimaging.

Near-Infrared Fluorescent Hydroxyapatite Nanoparticles for Targeted Photothermal Cancer Therapy.

Near-infrared (NIR) fluorophores have attracted great attention due to their excellent optical and photothermal properties. Among them, a bone-targeted NIR fluorophore (named P800SO3) contains two phosphonate groups, which play important roles in binding with hydroxyapatite (HAP) as the main mineral component of bones. In this study, biocompatible and NIR fluorescent HAP nanoparticles functionalized with P800SO3 and polyethylene glycol (PEG) were readily prepared for tumor-targeted imaging and photothermal therapy (PTT). The PEGylated HAP nanoparticle (HAP800-PEG) demonstrated improved tumor targetability with high tumor-to-background ratios (TBR). Moreover, the HAP800-PEG also showed excellent photothermal properties, and the temperature of tumor tissue reached 52.3 °C under NIR laser irradiation, which could completely ablate the tumor tissue without recurrence. Therefore, this new type of HAP nanoparticle has great potential as a biocompatible and effective phototheranostic material, which enables the use of P800SO3 for targeted photothermal cancer treatment.