Wang Aihui, Li Hongyan, Feng Hao, Qiu Huimin, Huang Rimei, Wang Yiqin, Ji Shichen, Liang Hong, Shen Xing-Can, Jiang Bang-Ping
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin541004, P. R. China.
ACS Appl Mater Interfaces. 2023 Feb 1;15(4):5870-5882. doi: 10.1021/acsami.2c19927. Epub 2023 Jan 23.
Natural biopolymers can be controllably synthesized in organisms and play important roles in biological activities. Inspired by this, the manipulation of biosynthesis of functional polymers will be an important way to obtain materials for meeting biological requirements. Herein, biosynthesis of functional conjugated polymer at the tumor site was achieved via the utilization of specific tumor microenvironment (TME) characteristics for the first time. Specially, a water-soluble aniline dimer derivative (-(3-sulfopropyl) -aminodiphenylamine, SPA) was artfully polymerized into polySPA (PSPA) nanoparticles at the tumor site, which was activated via the catalysis of hydrogen peroxide (HO) overexpressed in TME to produce hydroxyl radical (•OH) by coinjected horseradish peroxidase (HRP). Benefiting from outstanding near-infrared (NIR)-II absorption of PSPA, the polymerization process can be validly monitored by photoacoustic (PA) signal at the NIR-II region. Meanwhile, polymerization would induce the size of polymeric materials from small to large, improving the distribution and retention of PSPA at the tumor site. On the combination of NIR-II absorption of PSPA and the size variation induced by polymerization, such polymerization can be applied for tumor-specific NIR-II light mediated PA image and photothermal inhibition of tumors, enhancing the precision and efficacy of tumor phototheranostics. Therefore, the present work opens the way to manipulate TME-activated biosynthesis of functional conjugated polymer at the tumor site for overcoming formidable challenges in tumor theranostics.
天然生物聚合物可在生物体内可控合成,并在生物活性中发挥重要作用。受此启发,操纵功能聚合物的生物合成将成为获取满足生物需求材料的重要途径。在此,首次利用特定肿瘤微环境(TME)特征在肿瘤部位实现了功能共轭聚合物的生物合成。具体而言,一种水溶性苯胺二聚体衍生物(-(3-磺丙基)-氨基二苯胺,SPA)在肿瘤部位巧妙地聚合成聚SPA(PSPA)纳米颗粒,通过共注射辣根过氧化物酶(HRP),在TME中过表达的过氧化氢(HO)催化下产生活性羟基自由基(•OH)使其活化。得益于PSPA出色的近红外(NIR)-II吸收特性,聚合过程可通过NIR-II区域的光声(PA)信号有效监测。同时,聚合会使聚合物材料的尺寸由小变大,改善PSPA在肿瘤部位的分布和滞留。基于PSPA的NIR-II吸收特性与聚合诱导的尺寸变化相结合,这种聚合可应用于肿瘤特异性NIR-II光介导的PA成像和肿瘤的光热抑制,提高肿瘤光诊疗的精准度和疗效。因此,本研究为在肿瘤部位操纵TME激活的功能共轭聚合物生物合成开辟了道路,以克服肿瘤诊疗中面临的巨大挑战。