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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.

A tumor-targeted near-infrared (NIR) fluorophore CA800Cl was developed based on commercially available IR-786 by modulating its physicochemical properties. IR-786, a hydrophobic cationic heptamethine cyanine fluorophore, was previously recognized as a mitochondria-targeting NIR agent with excellent optical properties. Owing to the poor tumor specificity of IR-786 itself, in vivo studies on tumor-targeted imaging have not yet been investigated. A chloro-cyclohexene ring and indolium side groups on the heptamethine chain are key structural features that improve tumor targetability, owing to better biodistribution and clearance. Thus, IR-786 should be designed to be more soluble in aqueous solutions so that it can preferentially accumulate in the tumor based on the structure-inherent targeting strategy. In this study, we developed a bifunctional NIR fluorophore CA800Cl by incorporating carboxylate moieties in the basic structure of IR-786. This improved its tumor targetability and water solubility, thereby enabling the use of CA800Cl for enhanced photothermal cancer therapy.

ZW800-1, a representative zwitterionic near-infrared (NIR) fluorophore, can minimize background tissue uptake owing to its balanced surface charges, and therefore, is widely used for improved NIR fluorescence imaging. As ZW800-1 has no tumor targetability, tumor imaging is highly dependent on the ability of the molecules conjugated to the ZW800-1. To enable tumor targeting using ZW800-1 without additional conjugation, we developed a tumor-targetable and renal-clearable ZW800-1 analog (ZW800-AM) based on the structural modification of ZW800-1. Specifically, an amine group on the center linker of the ZW800-1 indocyanine backbone was modified by replacing phenoxypropionic acid with tyramine linkage on the meso-chlorine atom. This modification improved the tumor targeting ability, which is known as the structure-inherent targeting strategy. More importantly, ZW800-AM not only showed sufficient tumor accumulation without nonspecific uptake but also produced a photothermal effect, killing tumor cells under 808 nm NIR laser irradiation. In addition, ZW800-AM exhibited rapid renal elimination from the body within 4 h of injection, similar to ZW800-1. Overall, the discovery of ZW800-AM as a bifunctional phototherapeutic agent may provide an ideal alternative for tumor-targeted imaging and phototherapy.

Fabry disease is a rare lysosomal storage disorder resulting from the lack of α-Gal A gene activity. Globotriaosylceramide (GB3, ceramide trihexoside) is a novel endogenous biomarker which predicts the incidence of Fabry disease. At the early stage efficacy/biomarker study, a rapid method to determine this biomarker in plasma and in all relevant tissues related to this disease simultaneously is required. However, the limited sample volume, as well as the various levels of GB3 in different matrices makes the GB3 quantitation very challenging. Hereby we developed a rapid method to identify GB3 in mouse plasma and various tissues. Preliminary stability tests were also performed in three different conditions: short-term, freeze-thaw, long-term. The calibration curve was well fitted over the concentration range of 0.042–10 μg/mL for GB3 in plasma and 0.082–20 μg/g for GB3 in various tissues. This method was successfully applied for the comparison of GB3 levels in Fabry model mice (B6;129-Glatm1Kul/J), which has not been performed previously to the best of our knowledge.

A liquid chromatography–quadrupole time-of-flight (Q-TOF) mass spectrometric method was developed for early-stage research on adalimumab in rats. The method consisted of immunoprecipitation followed by tryptic digestion for sample preparation and LC-QTOF-MS/MS analysis of specific signature peptides of adalimumab in the positive ion mode using electrospray ionization. This specific signature peptide is derived from the complementarity-determining region (CDR) of adalimumab. A quadratic regression (weighted 1/concentration), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range of 1–100 μg/mL for adalimumab. The qualification run met the acceptance criteria of ±25% accuracy and precision values for quality control (QC) samples. This qualified LC-QTOF-MS/MS method was successfully applied to a pharmacokinetic study of adalimumab in rats as a case study. This LC-QTOF-MS/MS approach would be useful as a complementary method for adalimumab or its biosimilars at an early stage of research.