Nitric oxide (NO) is an important signaling molecule involved in many physiological and pathological processes. To understand these NO-mediated processes, it is a key to develop rapid and specific detection methods for NO. In the past 2 decades, numerous excellent fluorescent probes for NO have been designed; however, it still remains limitations such as slow response, low selectivity, and short excitation wavelength (<600 nm). In this Article, a two-photon fluorescent probe, NO-QA5, has been developed with 3-dimethylaminophenyl linking at the 6-position of 5-aminoquinoline as both the active site and prefluorophore for detection of NO. The nonfluorescent NO-QA5 can fast react with NO via a diazonium intermediate to generate two azoic regioisomers, one of which exhibits intramolecular charge transfer (ICT) emission, and two-photon absorption behavior (δΦ = 57 GM), giving a turn-on fluorescence rapid response. The sensing reaction is pH-insensitive in the range of 6-11 and highly selective and well sensitive (LOD = 15 nM), possible undergoing the same intermediate diazonium with the reaction under diazotization condition (NaNO/HCl). Also, as a nitrite fluorescent probe NO-QA5 exhibits highly sensitive (LOD = 7 nM). Therefore, NO-QA5 can serve as a dual functional fluorescent probe for NO and NO. Furthermore, NO-QA5 as a specific imaging agent has been demonstrated by achieving both exogenous and endogenous detections of NO in living cells under both one- and two-photon excitation and high resolution in tissue slices under two-photon excitation.
We have synthesized a new fluorophore with an absorption maximum at 650–660 nm, and constructed two deep red fluorescent probes, which are two ethers composed of a 2,4-dinitrobenzenoxy and B-Bodipy moiety.
Although enormous success has been obtained for dendritic cells (DCs)‐mediated antigen‐specific T cells anticancer immunotherapy in the clinic, it still faces major challenging problems: insufficient DCs in tumor tissue and low response rate for tumor cells lacking antigen expression, especially in low immunogenic tumors such as pancreatic cancer. Here, these challenges are tackled through tumor microenvironment responsive nanogels with prominent tumor‐targeting capability by Panc02 cell membranes coating and inhibition of tumor‐derived prostaglandin E2 (PGE2), aimed at improving natural killer (NK) cells activation and inducing activated NK cells‐dependent DCs recruitment. The engineered nanogels can on‐demand release acetaminophen to inhibit PGE2 secretion, thus promoting the activity of NK cells for non‐antigen‐specific tumor elimination. Furthermore, activated NK cells can secrete chemokines as CC motif chemokine ligand 5 and X‐C motif chemokine ligand 1 to recruit immature DCs, and then promote DCs maturation and induce antigen‐dependent CD8+ T cells proliferation for enhancing antigen‐specific immunotherapy. Notably, these responsive nanogels show excellent therapeutic effect on Panc02 pancreatic tumor growth and postsurgical recurrence, especially combination of the programmed cell death‐ligand 1 checkpoint‐blockade immunotherapy. Therefore, this study provides a simple strategy for enhancing low immunogenic tumors immunotherapy through an antigen‐independent way and antigen‐dependent way synergetically.
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