【Angew.Chem.】香港大学刘俊治|光热效率高达83.6%！原子精准BN掺杂开壳层材料，实现肿瘤高效光热治疗#

FIGURE 1 (a) Typical organic PTAs based on donor–acceptor systems. (b) Previously reported non-bonded BN-doped polycyclic hydrocarbon for PTT. (c) Our strategy. (d) Schematic illustration of water-dispersed radicaloid nanoparticles (BN-Dira and BN-Tetra) with boosted PCE for enhanced PTT (This work). (e) Comprehensive comparison of the PCE based on organic PTAs in recent years.#

FIGURE 2 (a) Synthetic routes toward two polycyclic hydrocarbons BN-Dira and BN-Tetra. Reaction conditions: a: HI, toluene, 1100C, 12 h, 50%; b: BBr3, MesMgBr, toluene, 110°C, 12 h, 30%; c: (2-Formylphenyl)boronic acid, Pd(PPh3)4, K2CO3, dioxane/H2O, 24 h, 50%; d: (1) MesMgBr, THF, (2) BF3•OEt2, DCM, 80%; e: t-BuOK, THF, 80%; f: 2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isophthalaldehyde, Pd(OAc)2, SPhos, K3PO4, dioxane/H2O, 900C, 12 h, 40%. (b) Single-crystal structure and bond length of BN-Dira. (c) Single-crystal structure and bond length of BN-Tetra.#

在物理性质表征阶段，电子顺磁共振（ESR）测试揭示了这两种分子鲜明的自由基特征。实验数据表明，BN-Dira表现出显著的双自由基特性，其自由基指数$y_0$达到0.74；而更为复杂的BN-Tetra则具有独特的四自由基性质，其自旋指数分别为$y_0 = 0.43$和$y_1 = 0.30$。这种高阶自由基特性赋予了材料在近红外区（NIR）极强的吸光能力。通过理论计算与实验光谱分析发现，由于BN单元的引入，分子的单重态-三重态能隙被有效压缩，这种窄能隙结构不仅有利于捕获低能量的近红外光子，更促进了激发态能量通过振动弛豫转化为热能。

FIGURE 3 (a) Calculated HOMA values, (b) calculated NICS (0) values, (c) the diamagnetic (clockwise), and paramagnetic (counterclockwise) ring currents under a magnetic field parallel to the z-axis are highlighted by red and blue arrows in AICD plots, and (d) calculated spin distribution map of BN-Dira and BN-Tetra.#

FIGURE 4 VT-1H-NMR spectra of (a) BN-Dira and (b) BN-Tetra in the aromatic region. VT-EPR spectra of the microcrystalline samples of (c) BN-Dira and (d) BN-Tetra. (e) Absorption spectra of two PHs in dichloromethane solution (10 µM). (f) Cyclic voltammetry measurements of two PHs.#

FIGURE 5 (a) Temperature–time profiles of BN-Dira NPs (0.50 mg/mL) under 808 nm laser irradiation with varying power. (b) Temperature–time profiles of BN-Dira NPs at different concentrations under 808 nm laser (0.8 W/cm2) irradiation. (c) Photothermal stability monitoring of BN-Dira NPs (0.50 mg/mL) under 808 nm laser irradiation (0.8 W/cm2). (d) Temperature–time profile of BN-Dira NPs aqueous solution (0.50 mg/mL) after 5 min of 808 nm laser (0.8 W/cm2) irradiation and subsequent cessation. (e) Calculation of photothermal conversion efficiency of BN-Dira NPs. (f) Infrared thermal imaging of BN-Dira NPs at various concentrations under 808 nm laser irradiation (0.8 W/cm2). (g) Infrared thermal imaging of BN-Dira NPs (0.50 mg/mL) under 808 nm laser irradiation at different power levels.#

核心的光热性能评估在得到了详尽展示。研究人员将制备好的BN掺杂分子封装在生物相容的纳米胶束中，并在808 nm激光照射下监测温度变化。令人振奋的是，四自由基物种BN-Tetra表现出了惊人的产热能力，其光热转化效率最终计算为83.6%，这一数值远高于目前报道的大多数纯有机光热剂。此外，在经历多次激光照射循环后，溶液的升温曲线依然保持高度一致，充分证明了该分子在极端光照条件下的优异光化学稳定性，消除了临床治疗中常见的有机物易光漂白的顾虑。

FIGURE 6 (a) Cytotoxicity of BN-Dira NPs and (b) BN-Tetra NPs toward 4T1 cells under 808 nm laser irradiation (1.0 W/cm2), and (c) DAPI/PI staining images of 4T1 cells subjected to different treatments. The data are shown as the mean ± SD from a representative experiment of two to three independent experiments with n = 4 biologically independent samples per group (a, b). Statistical significance was calculated via unpaired Student’s t test (two tailed) comparing laser off vs. laser on at the same material concentration, with **** indicating p < 0.0001.#

FIGURE 7 (a) Temperature change curves of tumor regions in mice under 808 nm laser irradiation (1.0 W/cm2) after different treatments over 96 h. (b) Temperature change curves of tumor regions in mice under 808 nm laser irradiation (1.0 W/cm2) after different treatments, monitored continuously for 5 min. (c) Photothermal imaging of tumor regions in mice under 808 nm laser irradiation (1.0 W/cm2) after different treatments over 96 h. (d) Photothermal imaging of tumor regions in mice under 808 nm laser irradiation (1.0 W/cm2) after different treatments, monitored continuously for 5 min. (e) Temperature change curve of tumor regions in mice injected with PBS under 808 nm laser irradiation (1.0 W/cm2). (f) Temperature change curve of tumor regions in mice injected with BN-Dira NPs under 808 nm laser irradiation (1.0 W/cm2). (g) Temperature change curve of tumor regions in mice injected with BN-Tetra NPs under 808 nm laser irradiation (1.0 W/cm2).#

FIGURE 8 (a) Schematic diagram of the experimental design for photothermal therapy efficacy validation in tumor-bearing mouse models. (b) Trends in relative body weight of mice. (c) Trends in relative tumor volume of mice. (d) Tumor weight in different treatment groups. (e) HE staining and TUNEL staining images (green) of tumors in different treatment group. The data are shown as the mean ± SD from a representative experiment with n = 4 biologically independent samples per group (b to d). Statistical significance was calculated via one-way ANOVA in (d) with Bonferroni multiple comparisons posttest, where ns indicates no statistical significance and *** indicates p < 0.001.#

最后的生物学实验进一步印证了该材料的临床应用潜力。体外细胞实验证实，BN-Tetra纳米颗粒在激光诱导下能迅速通过高温引发癌细胞凋亡，而无光照组则表现出极佳的细胞安全性。在小鼠肿瘤模型中，研究团队通过静脉注射给药，并在肿瘤区域施加精准的近红外照射。实验结果显示，治疗组的肿瘤在短时间内被完全消除，且小鼠的体重与各项生理指标均未出现异常。这一结果强有力地证明了原子精准BN掺杂策略在实现高效肿瘤铲除的同时，能保持极低的系统性毒副作用。