Gao Xingxing, Li Jingjing, Li Xiaoxu, Yin Xing, Cao Shunze, Pu Ximing, Wang Juan, Liao Xiaoming, Huang Zhongbing, Yin Guangfu
College of Biomedical Engineering, Sichuan University, Chengdu 610065, Sichuan, China.
West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
ACS Appl Mater Interfaces. 2025 Jun 18;17(24):35205-35220. doi: 10.1021/acsami.5c05572. Epub 2025 Jun 3.
Polydopamine (PDA) possesses potential as a photothermal agent for tumor treatment owing to its photothermal capacity, chemical modifiability, excellent biocompatibility, and selective biodegradability. However, weak near-infrared (NIR) light absorption seriously hinders its actual utilization, especially in NIR-II. This study presents a novel molecularly modified PDA with remarkably increased NIR absorption and remarkably enhanced photothermal conversion capacity in both NIR-I and NIR-II. Dopamine monomers are covalently bound with elaborately selected 2,6-pyridinedicarboxylic acid (DPA) through an amidation reaction and then undergo an oxidative polymerization to form DPA-doped PDA nanoparticles (DPA-PDA NPs). By constructing donor-acceptor pairs and extending the conjugation length of molecular units, the energy band gap of DPA-PDA between the highest occupied molecular orbital and the lowest unoccupied molecular orbital is diminished from 0.77 to 0.45 eV, facilitating the electron low-energy transition. Meanwhile, the content of carbon-centered free radicals is obviously raised via suppressing their dimerization and quenching by the conjugation effect and steric hindrance effect, where the strengthened electron spin and vibration may promote charge and energy transfers, increasing and accelerating the excited electron nonradiative decay. As a result, the DPA-PDA NPs exhibit the enhanced NIR light absorption (196 and 205% over PDA) and much higher photothermal conversion efficiency (1.4 and 2.1 times that of PDA) under 808 and 1064 nm irradiation, respectively, achieving more effective tumor cells inhibition and tumor ablation . Interestingly, photothermal therapies with DPA-PDA for tumor-bearing mice emerge with higher tumor elimination (nearly 100%) under 1064 nm irradiation than that under 808 nm irradiation (94.3%), without recurrence within 20 days, which is attributed to both the enhanced photothermal capacity of DPA-PDA and the stronger tissue penetration ability of NIR-II. This design provides a new option to enhance the photothermal capacity of polydopamine as an applicative photothermal agent for tumor therapy.
聚多巴胺（PDA）因其光热能力、化学可修饰性、优异的生物相容性和选择性生物降解性而具有作为肿瘤治疗光热剂的潜力。然而，其近红外（NIR）光吸收较弱严重阻碍了其实际应用，尤其是在近红外二区（NIR-II）。本研究提出了一种新型的分子修饰聚多巴胺，其在近红外一区（NIR-I）和近红外二区的近红外光吸收显著增加，光热转换能力显著增强。多巴胺单体通过酰胺化反应与精心选择的2,6-吡啶二甲酸（DPA）共价结合，然后进行氧化聚合形成DPA掺杂的聚多巴胺纳米颗粒（DPA-PDA NPs）。通过构建供体-受体对并延长分子单元的共轭长度，DPA-PDA在最高占据分子轨道和最低未占据分子轨道之间的能带隙从0.77 eV减小到0.45 eV，有利于电子的低能跃迁。同时，通过共轭效应和空间位阻效应抑制碳中心自由基的二聚化和猝灭，明显提高了碳中心自由基的含量，其中增强的电子自旋和振动可能促进电荷和能量转移，增加并加速激发电子的非辐射衰变。结果，DPA-PDA NPs在808和1064 nm照射下分别表现出增强的近红外光吸收（比PDA分别高出196%和205%）和更高的光热转换效率（分别是PDA的1.4倍和2.1倍），实现了更有效的肿瘤细胞抑制和肿瘤消融。有趣的是，用DPA-PDA对荷瘤小鼠进行光热治疗时，在1064 nm照射下比在808 nm照射下（94.3%）出现更高的肿瘤消除率（近100%），且在20天内无复发，这归因于DPA-PDA增强的光热能力和近红外二区更强的组织穿透能力。该设计为增强聚多巴胺作为肿瘤治疗应用光热剂的光热能力提供了新的选择。
