Heptamethine Cyanine Dyes with Ultra‐Efficient Excited‐State Nonradiative Decay for Synergistic Photothermal Immunotherapy

Abstract

Organic dyes in the excited singlet state (S1) decay via intersystem crossing (ISC) to the triplet state, radiative dissipation as fluorescence, or nonradiative decay for thermal deactivation. Although many studies are conducted to improve ISC and fluorescence efficiency, few have optimized S1 decay via thermal deactivation, which is crucial for designing photothermal agents. A strategy for inhibiting radiative decay and ISC by introducing electron withdraw groups (EWGs) into the meso position of heptamethine cyanines (Cy7) is reported here, which allows S1 energy decay via nonradiative relaxation. The decrease in the electron density of Cy7 caused by EWGs improved the photostability, which is important for biological applications because conventional cyanine dyes are easily photobleached. The EWG substitutes acted as efficient rotation groups with low‐energy barriers, narrowing the energy gap between S1 and the ground state and considerably improving the photothermal conversion efficiency (PCE). The PCE of CF3cy with the strongest EWG is increased up to 83%. Liposome is used as a carrier to improve the biocompatibility and tumor retention of CF3cy, which is combined with the toll‐like receptor agonist resiquimod (R848) for synergistic photothermal immunotherapy against both primary and distant tumors and elicits a long‐lasting immunological memory effect.

Rational design of a lysosome-targeted fluorescent probe for monitoring the generation of hydroxyl radicals in ferroptosis pathways

“…Indole salt derivative (compound 1 in Scheme S1 † ) was first prepared using the reported methods. 47 Then, the solution of 15 mL anhydrous ethanol containing compound 1 (400 mg, 1.27 mmol) and 4-morpholinobenzaldehyde (267 mg, 1.40 mmol) was stirred under reflux at 80 °C for 12 h. After cooling to room temperature, the solvent was evaporated in a vacuum, and the crude product was purified by silica gel chromatography (200–300 mesh) using CH 2 Cl 2 /CH 3 OH (20 : 1, v/v) as the eluent to obtain HCy-OH as a dark red solid (350 mg, 56% yield). m.p.…”

Aggregation‐enhanced photothermal therapy of organic dyes

“…Organic photothermal dyes encompass a range of molecules such as cyanines (Bhattarai & Dai, 2017; Xia et al, 2023a), phthalocyanines (Li, Park, et al, 2020; Zheng et al, 2021), boron dipyrromethene (BODIPY) (Ma et al, 2021; Schneider et al, 2023), perylenediimide (PDI) derivatives (Li, Liu, et al, 2020; Liu, Ji, et al, 2021; Liu, Li, Ma, et al, 2022), and AIEgens (Li, Wang, et al, 2023; Liu, Li, et al, 2021; Wang, Chen, et al, 2021; Wang, Yu, et al, 2022). Various chemical modification strategies have been developed to enhance the PCE of these dye molecules.…”

“…The ACQ process involves complex photophysical mechanisms, including intermolecular energy transfer, enhanced electronic state coupling, and exciton formation, collectively promoting non‐radiative relaxation pathways and ultimately increasing heat generation (Luo et al, 2001; Mei et al, 2015). Additionally, dye aggregation can also inhibit photodynamic processes, redirecting the energy conversion from light to heat instead of chemical processes (Xia et al, 2023b). This enhancement of non‐radiative dissipation due to aggregation is commonly observed in different molecular packing modes, including random aggregates and specific aggregation states such as H‐aggregates and J‐aggregates.…”

Immunogenic Cell Death Induction and Oxygenation by Multifunctional Hollow Silica/Copper-Doped Carbon Dots

“…Angiogenesis factors induced by hypoxia environment promote tumor cells to infiltrate more efficiently and metastasize to distant areas. − Both chemodynamic therapy (CDT) and photodynamic therapy (PDT) are selective therapies mediated by reactive oxygen species − which can induce immunogenic cell death (ICD) by damaging cells under endogenous and exogenous stimuli, and the tumor microenvironment changes from immunosuppressive to antitumor, triggering systemic immune activity. PDT and CDT combining with immunotherapy adjuvant can inhibit tumor metastasis. − However, although the combination of ICD and immunotherapy adjuvant has achieved many significant effects, the ICD induced by PDT or CDT alone is generally weak. Therefore, enhancing ICD has become the focus of attention.…”