Activatable self-assembled organic nanotheranostics: Aspartyl aminopeptidase triggered NIR fluorescence imaging-guided photothermal/photodynamic synergistic therapy.

Phototherapy has developed as a powerful method for remedial modalities. The conventional photosensitizers are "always on" state and lack tumor targeting, which contributed to poor therapeutic effect and high toxicity. Therefore, we developed an aspartyl aminopeptidase (DNPEP) activated self-assembled organic nanoparticles (NRh-Asp NPs) with sensitive external irradiation-induced photothermal therapy and photodynamic therapy (PTT/PDT). NRh-Asp NPs can be activated to NRh-NH2 NPs by DNPEP, demonstrating strong near-infrared (NIR) fluorescence, and efficiently generating heat and singlet oxygen under the near-infrared laser. NRh-Asp NPs was successfully used for visualizing DNPEP in vitro and in vivo in NIR region, and demonstrated good synergistic anti-cancer efficacy of PDT and PTT. These results suggest that DNPEP-mediated NRh-Asp NPs are promising candidates for image-guided phototherapeutic of tumor.

Bioluminescence imaging of fibroblast activation protein-alpha in vivo and human plasma with highly sensitive probe.

Fibroblast activation protein-alpha (FAPα) has emerged as a biomarker of tumor stromal fibroblasts. FAP was overexpressed in stromal fibroblasts of human malignancies and positively correlated with the depth of tumor invasion, lymphatic metastasis, distant metastases, high TNM stage and poor prognosis. However, the circulating FAP levels in the plasma of gastric cancer patients and the relationship between FAP levels and gastric cancer remain unknown. Moreover, probes with super selectivity, extremely high sensitivity, and excellent performance in quantitative detection are still lacking. Herein, we developed the bioluminescent probe BL-FAP for sensitive detection and imaging of endogenous FAP in gastric cancer cells and tissues and plasma from gastric cancer patients. The probe exhibited the high signal-to-noise ratio (15000∼fold), the excellent selectivity (FAP/DPP IV ratio and FAP/PREP ratio = 50000∼ fold), and the high sensitivity (18.1 pg/mL). BL-FAP facilitates monitoring of endogenous FAP in living cells and nude mice bearing MGC-803-luc tumors. More importantly, this probe was successfully applied to the measurement of FAP activity levels in plasma from gastric cancer patients for the first time. A significant enhancement in FAP levels was observed in patients with gastric cancer, suggesting that the FAP level may be a potential diagnostic parameter for gastric cancer.

Bioluminescence Imaging of Selenocysteine in Vivo with a Highly Sensitive Probe.

Selenocysteine (Sec), a vital member of reactive selenium species, is closely implicated in diverse pathophysiological states, including cancer, cardiovascular diseases, diabetes, neurodegenerative diseases, and male infertility. Monitoring Sec in vivo is of significant interest for understanding the physiological roles of Sec and the mechanisms of human diseases associated with abnormal levels of Sec. However, no bioluminescence probe for real-time monitoring of Sec in vivo has been reported. Herein, we present a novel bioluminescent probe BF-1 as an effective tool for the determination of Sec in living cells and in vivo for the first time. BF-1 has advantages of high sensitivity (a detection limit of 8 nM), remarkable bioluminescence enhancement (580-fold), reasonable selectivity, low cytotoxicity, and high signal-to-noise ratio imaging feasibility of Sec in living cells and mice. More importantly, BF-1 affords high sensitivity for monitoring Sec stimulated by Na2SeO3 in tumor-bearing mice. These results demonstrate that our new probe could serve as a powerful tool to selectively monitor Sec in vivo, thus providing a valuable approach for exploring the physiological and pathological functions and anticancer mechanisms of selenium.