Panfei Xing

Less oxygen‐independent Type‐I reactive oxygen species (ROS) generated by photosensitizers offer distinct advantages for tumor photodynamic therapy (PDT). However, most conventional photosensitizers activate nonselective mixed ROS pathways, significantly hindering the advancement of PDT. In this study, we propose a synergistic molecular design strategy that integrates sulfur‐atom positioning and acceptor engineering to achieve preferential Type‐I ROS generation. We identified a novel near‐infrared Type‐I photosensitizer NS4 . Combined theoretical calculations and experimental characterizations demonstrate that sulfur substitution enhances the S ₁ ‐T ₁ intersystem crossing, while acceptor engineering promotes a pronounced twisted intramolecular charge transfer (TICT). This TICT effect lowers the energy of the S ₁ state and stabilizes the T ₁ state, thereby synergistically enabling the preferential production of Type‐I ROS. Both free NS4 derivative and NS‐NPs , self‐assembled from NS4 and F‐127, can generate substantial amounts of Type‐I ROS under 660 nm laser irradiation, effectively triggering tumor cell apoptosis. In vivo assessments confirm that a single dose of NS‐NPs significantly suppresses tumor growth with negligible systemic toxicity. This work establishes theoretical and structural guidelines for the rational design of high‐performance Type‐I photosensitizers and facilitates the further translation of PDT.

Polymethine dyes are invaluable tools for studying biological processes in vivo due to their superior fluorescence properties and biological functions. However, despite the availability of excellent polymethine dyes, their uncontrollable interactions with albumin often limits their applications to specialized contexts. In this study, we present a general strategy for modulating the albumin sensitivity of dyes through a hydrophilicity-differentiated bidirectional regulation approach. Experimental data and computational simulations demonstrate that sulfonate positioning is crucial for suppressing hydrophobic interaction-mediated albumin-dye binding. Furthermore, this effect is enhanced when coupled with an optimal length of the polymethine bridge, which governs the postbinding responsiveness of the dye. Together, these factors establish the regulatory basis for differentiating albumin-sensitive and insensitive dyes. Consequently, a hydrophilic and albumin-insensitive Cy5 was identified and constructed a probe, showing potential for detecting hepatic fibrosis in mice without albumin interference (a protein primarily produced in the liver). Conversely, an albumin-sensitive Cy5 was synthesized by reducing the hydrophilicity of a Cy5 framework with a high TICT tendency, which can monitor blood-brain barrier function in vivo.

Biothiols, essential sulfur-containing amino acids, play a critical role in various physiological processes in animals. Abnormal biothiol levels are closely associated with the onset and progression of numerous diseases, leading to increased research on their detection and quantification. While many fluorescent probes exist for biothiol tracking with a small Stokes shift, there is a scarcity of near-infrared (NIR) fluorescent probes with a large Stokes shift specifically for biothiols. This study introduces a new fluorescent probe, XB-F, based on the fluorinated NIR Rhodol. When biothiols are added, XB-F emits NIR light at 700 nm with a significant Stokes shift of 161 nm. The probe exhibits high sensitivity to biothiols, showing a 25-fold increase in fluorescence, along with excellent sensitivity and selectivity towards biothiols compared to other potential interferents in biological samples. Due to its low cytotoxicity, XB-F is suitable for detecting exogenous and endogenous biothiols in HepG-2 cells. Moreover, by utilizing its NIR emission with a large Stokes shift, XB-F is employed for monitoring biothiols in vivo. This innovative research opens avenues for further exploration into biothiol-related diseases, offering a valuable bioimaging tool for future studies.

Although fine particulate matter (FPM) in air pollutants and tobacco smoke is recognized as a strong carcinogen and global threat to public health, its biological mechanism for inducing lung cancer remains unclear. Here, by investigating FPM’s bioactivities in lung carcinoma mice models, we discover that these particles promote lung tumor progression by inducing aberrant thickening of tissue matrix and hampering migration of antitumor immunocytes. Upon inhalation into lung tissue, these FPM particles abundantly adsorb peroxidasin (PXDN) – an enzyme mediating type IV collagen (Col IV) crosslinking – onto their surface. The adsorbed PXDN exerts abnormally high activity to crosslink Col IV via increasing the formation of sulfilimine bonds at the NC1 domain, leading to an overly dense matrix in the lung tissue. This disordered structure decreases the mobility of cytotoxic CD8⁺ T lymphocytes into the lung and consequently impairs the local immune surveillance, enabling the flourishing of nascent tumor cells. Meanwhile, inhibiting the activity of PXDN abolishes the tumor-promoting effect of FPM, indicating the key impact of aberrant PXDN activity on the tumorigenic process. In summary, our finding elucidates a new mechanism for FPM-induced lung tumorigenesis and identifies PXDN as a potential target for treatment or prevention of the FPM-relevant biological risks.