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Heptamethine cyanines (Cy7) typically exhibit strong near-infrared (NIR) fluorescence signals when in monodisperse states, but their distinctive π-conjugated structure leads to limited solubility in aqueous solutions, ultimately resulting in inherent fluorescence self-quenching. Enhancing the fluorescence quantum yield of these agents within aqueous environments, in order to achieve high-resolution biological imaging, presents a significant challenge. Herein, a benzothiazole-based Cy7-derivative (Cy7-BTH) is developed, exhibiting unique H-aggregation properties in aqueous solutions. Bovine serum albumin (BSA) binds to Cy7-BTH (BSA@Cy7-BTH) to modulate its molecular stacking and energy transfer, boosting its fluorescence accompanied by bright NIR-II tail emission. The competitive binding alters the planarity of Cy7-BTH, restricting its intramolecular rotation, and simutaneously changes the conformation of BSA, leading to BSA@Cy7-BTH aggregation to form hierarchical-structured nanoparticles. Notably, the BSA@Cy7-BTH nanoparticles significantly enhanced photothermal response of Cy7-BTH while maintaining its controlled reactive oxygen species (ROS) generation, offering NIR-II imaging-guided surgical removal of primary tumors, and simultaneously inhibiting cancer cell metastasis by synergistic PDT/PTT dissection of metastatic tumor cells in sentinel lymph nodes (SLNs). This study provides an innovative but facile strategy for their potential clinical applications by precisely regulating the intermolecular competitive interactions of NIR theranostic agents. [Display omitted] • A molecular competition-based supramolecular strategy was proposed for high SNR imaging. • BSA binds to Cy7-BTH (BSA@Cy7-BTH) to modulate its molecular stacking and energy transfer. • BSA@Cy7-BTH offers NIR-II imaging-guided surgical removal of primary tumors. • Metastatic tumor cells in SLNs were dissected by synergistic PDT/PTT without side effects. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are the primary cause of organic nitrate drug tolerance and endothelial dysfunction. In order to scavenge the ROS and maintain the therapeutic effect of nitrates, we designed and synthesized ten new types of dual-acting nitrate molecules by combining NIT-type nitroxides and 5-ISMN. These included two types of novel epimeric nitroxide-nitrate conjugates (15(S) and 15(R)), which had pharmacophore connections. We also synthesized 8 NIT radicals without 5-ISMN in order to compare the activities of these novel nitric oxide donors. Several dual-acting nitroxide-based nitrate conjugates showed the ability to release NO and cause anti-oxidant effects in human umbilical vein endothelial cells. Among these conjugates, 15(S) showed the most prominent pro-vasodilative effect. In angiotensin II infusion-induced hypertensive mice, 15(S) treatment for 4 weeks decreased both the systolic and diastolic blood pressures and ameliorated the vascular endothelial and smooth muscle functions of isolated thoracic aortas. In addition, the vascular structure of the mice was restored and their vascular oxidative stress was decreased. The results suggest that these novel nitric oxide donors can be used as potential drugs in the treatment of vascular diseases. Therefore, the strategy of using a combination of antioxidants and NO-donors can be a promising way to develop novel organic nitrate drugs for future use in combating disease. [Display omitted] • Ten novel types of NO-donor molecules with antioxidative activity were synthesized, including epimers (15(S) and 15(R)). • 15(S) induced vasodilation without the induction of oxidative stress. • 15(S) treatment improved vascular function in Ang II-induced hypertensive mice. [ABSTRACT FROM AUTHOR]