NQO-1 Enzyme-Activated NIR Theranostic Agent for Pancreatic Cancer

Abstract

Pancreatic cancer (PC) is one of the most lethal cancers worldwide, which is usually diagnosed in the advanced stage and is highly resistant to traditional chemotherapy, radiotherapy, and immunotherapy. Therefore, there is an urgent need for developing new PC-specific imaging and treatment. In this study, an quinone oxidoreductase 1 (NQO-1)-activated near-infrared (NIR) agent, ICy-Q, was synthesized. ICy-Q is almost nonemissive, while its NIR emission at 705 nm is triggered by NQO-1-induced reduction in the PC cells. In addition, the reduction product, ICy-OH, is specifically enriched in mitochondria and lysosomes and acts as an effective chemotherapeutic agent to selectively induce pancreatic cancer cell death via the cell pyroptosis pathway. Further studies have shown that ICy-Q is suitable for ex vivo imaging of clinical PC sections and solid tumors from patients. We expect this study will be helpful in the future for the design of targeted theranostic agents for PC.

Lysosome-Anchoring Activation Design of Type I Photosensitizer Evokes Pyroptosis and Antitumor Immunity

“…Consistent with the results of in vitro experiments (Figure S22b), the ENBS plus irradiation group (20.3%) possessed the highest induction of DCs’ maturation compared to all other treatments (Figure a and Figure S31), which was 2.46- and 2.80-fold higher than that observed in the presence of the ENBS group (8.24%) and PBS group (7.26%), respectively. As is well-known, CD8 + cytotoxic T lymphocytes (CTLs) (CD8 + T cells) can kill cancer cells by releasing cytotoxins, which play essential roles in the antitumor immune response. − Moreover, helper T cells (CD4 + T cells) are critical in regulating adaptive immunity. , Therefore, the helper T cells (CD4 + ) and cytotoxic T cells (CD8 + ) in the spleen after different treatments were analyzed by flow cytometry (Figures S32–S33). As shown in Figure b-c, the ENBS-mediated treatment group significantly improved the proportion of CD4 + and CD8 + T cells.…”

“…69−72 Moreover, helper T cells (CD4 + T cells) are critical in regulating adaptive immunity. 38,39 Therefore, the helper T cells (CD4 + ) and cytotoxic T cells (CD8 + ) in the spleen after different treatments were analyzed by flow cytometry (Figures S32−S33). As shown in Figure 5b-c, the ENBS-mediated treatment group significantly improved the proportion of CD4 + and CD8 + T cells.…”

Construction and comprehensive analysis of a novel prognostic signature associated with pyroptosis molecular subtypes in patients with pancreatic adenocarcinoma

“…In studies related to PAAD, Cui et al that MST1 inhibits pancreatic cancer progression via ROS-induced pyroptosis (56). Peng et al showed that ICy OH produced by ICy Q could damage mitochondrial membranes, induce intracellular inflammatory responses, and selectively induce pancreatic cancer cell death via the cell pyroptosis pathway (a series of enzymatic reactions leading to the production of fragments of pyroptosis protein GSDMD-N) (57).…”

Shedding light on ONOO− detection: the emergence of a fast-response fluorescent probe for biological systems

“…This advanced imaging modality can efficiently detect ONOO À in situ in vivo, while simultaneously offering benefits such as high sensitivity, non-invasiveness, ease of operation, excellent selectivity, and high efficiency. [26][27][28][29][30] In light of these advantages, we intend to design and synthesize a stable fluorescence sensor that can precisely and exclusively identify ONOO À in living cells, tissues, or organisms.…”