【Adv.Mater.】大连理工彭孝军院士课题组孙文|系间窜跃提速2个数量级！超快5皮秒光敏剂自适应调控激发态，肿瘤抑制率达91.3%#

SCHEME 1 (a) The excited state process of PSs based on (I) Heavy atom effect, (II) the SOCT-ISC mechanism, and (III) introducing a carbonyl group. (b) The structure and the excited state process of Cy5-PCZ, and the schematic diagram illustrating the inhibition of tumor growth and lung metastasis by Cy5-PCZ under light irradiation.#

FIGURE 1 (a) The structures of different meso-Cy5 molecules. (b) Photophysical data of different meso-Cy5 molecules (3 µM). (c) Absorption spectra and (d) fluorescence spectra of different molecules (3 µM) in H2O. (e) The ESR signals of ROS generated by Cy5-PCZ before and after light irradiation. (f) Comparison of ABDA absorbance changes at 378 nm with meso-Cy5 molecules (5 µM) in H2O on different times (660 nm, 4 mW/cm2) (n = 3). (g) Comparison of DHE fluorescence intensity changes at 580 nm of meso-Cy5 molecules (5 µM) in H2O on different times (660 nm, 4 mW/cm2) (n = 3). (h) Comparison of HPF fluorescence intensity changes at 514 nm of meso-Cy5 molecules (5 µM) in H2O on different times (660 nm, 4 mW/cm2) (n = 3). I. Maximum absorption wavelength (nm); II. Maximum emission wavelength (nm); III. Molar absorption coefficient yield, 104 M−1 cm−1; IV. Absolute fluorescence quantum yield.#

FIGURE 2 fs-TAS of (a) Cy5-H, (b) Cy5-B, (c) Cy5-Br, and (d) Cy5-PCZ in H2O. (e) Magnified view of the fs-TAS (430–550 nm) of Cy5-PCZ. (f) Magnified view of the fs-TAS (550–720 nm) of Cy5-PCZ. (g) Kinetic traces of Cy5-PCZ at selected wavelengths. (h) Evolution-associated difference spectra (EADS) of Cy5-PCZ obtained from global fitting analysis. (i) Concentration evolution of Cy5-PCZ in H2O.#

FIGURE 3 (a) Molecular structure and optimized geometric configuration of Cy5-H, Cy5-B, Cy5-Br, and Cy5-PCZ. (b) Energy level levels of different molecules in H2O. (c) Frontier orbital diagrams of different molecules in H2O. (d) Schematic diagram of the a-PET and the energy gap of different molecules. (e) The energy and the possible excited state processes in different molecules.#

生物实验进一步证实了其卓越的临床转化潜力。Cy5-PCZ凭借阳离子特性特异性靶向细胞线粒体，光照下引发线粒体严重损伤。这种强氧化应激在常氧和低氧环境下均能高效诱导肿瘤细胞凋亡，并触发细胞焦亡与免疫原性损伤相关分子模式的释放。在荷瘤小鼠模型中，该光敏剂在注射后4小时展现出极佳的肿瘤富集效应，光照治疗后实现了高达91.3%的肿瘤抑制率。同时，原位乳腺癌小鼠实验表明，该疗法能显著阻断肿瘤的肺部转移，使小鼠60天生存率达到80%，且具备优异的生物安全性。

FIGURE 4 (a) Electron-hole distribution of different excited states of Cy5-H, Cy5-B, and Cy5-Br. (b) The electron-hole distribution of Cy5-PCZ in H2O. (c) Schematic diagram of the possible photochemical pathway of Cy5-PCZ. (d) Theoretical model of the electron transition and electron spin mechanism of Cy5-PCZ.#

FIGURE 5 (a) ROS imaging in 4T1 cells. (b) Cy5-PCZ co-localization fluorescence imaging analysis. (c) Fluorescence imaging of JC-1 stained 4T1 cells. Scale bar: 30 µm.#

FIGURE 6 Cytotoxicity of Cy5-PCZ against (a) 4T1, (b) HepG2, and (c) MCF-7 cells under normoxic conditions (21% O2). Cytotoxicity of Cy5-PCZ against (d) 4T1, (e) HepG2, and (f) MCF-7 cells under hypoxic conditions (2% O2). Calcein AM/PI staining in 4T1 cells under (g) normoxia (21% O2) and (h) hypoxia (2% O2). Scale bar: 100 µm. Error bars represent S.D. from the mean (n = 6).#

FIGURE 7 (a) Apoptosis detection of 4T1 cells under different treatments. (b) The proportion of apoptosis in normoxic (21% O2) conditions with different treatments. (c) The proportion of apoptosis in hypoxic (2% O2) conditions with different treatments. (d) 4T1 cells-stained Annexin-V/PI. Scale bar: 30 µm.#

FIGURE 8 (a) Schematic diagram of pyroptosis of 4T1 cells induced by Cy5-PCZ with light irradiation. (b) Morphological changes incubated with Cy5-PCZ. Scale bar: 20 µm. (c) CRT fluorescence imaging of 4T1 cells. Scale bar: 20 µm. (d) Fluorescence imaging of HMGB1 in 4T1 cells. Scale bar: 20 µm. (e) Extracellular LDH levels (n = 3). (f) ATP levels in 4T1 cells (n = 4). (g) GSDMD-N, Pro-Caspase-1, and Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) expression of 4T1 treated with different treatments. G1: Control, G2: Cy5-PCZ, G3+Light (60 min), G3+Light (90 min). Error bars represent S.D. from the mean. (Statistical significance: * p < 0.05, ** p ≤ 0.01, or *** p ≤ 0.001).#

FIGURE 9 (a) Mouse treatment flowchart. (b) In vivo fluorescence imaging of mice. (c) Relative fluorescence intensities of the tumor at different times. (n = 3). (d) Relative fluorescence intensities of major organs at different times (n = 3). (e) Changes in tumor volume of mice (n = 5). (f) The weight of the tumor isolated (n = 5). (g) The inhibition rates of tumors by different treatment methods (n = 5). (h) Changes in the body weight of mice (n = 5). (i) H&E staining, TUNEL staining, and Ki67 staining of tumor tissues. Scale bar: 50 µm. Error bars represent S.D. from the mean. (Statistical significance: * p < 0.05, ** p ≤ 0.01, or *** p ≤ 0.001).#

FIGURE 10 (a) Schematic of PDT inhibiting breast cancer lung metastasis in mice. (b) H&E staining of lung tissue. Scale: 100 µm. (c) Photographs of lung tissue. (d) Lung weight in different groups (n = 5). (e) Pulmonary metastatic nodules in different groups (n = 5). (f) Survival rate of mice after different treatments. Error bars represent S.D. from the mean. (Statistical significance: * p < 0.05, ** p ≤ 0.01, or *** p ≤ 0.001).#