Hu Chunling, Cai Lihan, Liu Sainan, Liu Ying, Zhou Ying, Pang Maolin
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, P. R. China.
University of Science and Technology of China, Hefei 230026, P. R. China.
Bioconjug Chem. 2020 Jun 17;31(6):1661-1670. doi: 10.1021/acs.bioconjchem.0c00209. Epub 2020 May 26.
Due to the specific tumor microenvironment (TME) and immunosuppressive state of cancer cells, conventional antitumor therapies face severe challenges, such as high rates of recurrence and metastasis. Herein, Cu-PPT nanoparticles were synthesized based on copper acetate, -phenylenediamine, and 5,10,15,20-tetra-(4-aminophenyl)porphyrin via oxidative coupling reaction for the first time, and the resultant product was used for synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT). The polymer nanoparticles exhibited excellent photodynamic and photothermal effect with a photothermal conversion efficacy of 40.1% under 650 and 808 nm laser irradiation, respectively. Encapsulated Cu(I)/Cu(II) ions permitted Cu-PPT with glutathione (GSH) peroxidase-mimicking, catalase-mimicking, and Fenton-like activity to regulate TME. Depletion of overexpressed GSH would reduce antioxidant capacity, generated O could relieve hypoxia for enhancing PDT, and hyperthermia from PTT could promote the yield of ·OH. This multifunctional nanosystem with cascade reactions could inhibit tumor growth and activate immune responses effectively. By further combining with antiprogrammed death-ligand 1 (anti-PD-L1) checkpoint blockade therapy, distant tumor growth and cancer metastasis were successfully suppressed.
由于癌细胞具有特定的肿瘤微环境（TME）和免疫抑制状态，传统的抗肿瘤疗法面临着严峻挑战，如高复发率和转移率。在此，首次通过氧化偶联反应，以醋酸铜、对苯二胺和5,10,15,20-四（4-氨基苯基）卟啉为原料合成了铜-卟啉聚合物纳米颗粒（Cu-PPT NPs），并将所得产物用于协同光热疗法（PTT）、光动力疗法（PDT）和化学动力疗法（CDT）。该聚合物纳米颗粒分别在650和808 nm激光照射下表现出优异的光动力和光热效应，光热转换效率分别为40.1%。封装的Cu（I）/Cu（II）离子使Cu-PPT NPs具有谷胱甘肽（GSH）过氧化物酶模拟、过氧化氢酶模拟和类芬顿活性，从而调节TME。过表达的GSH消耗会降低抗氧化能力，产生的O₂可缓解缺氧以增强PDT，PTT产生的热疗可促进·OH的产生。这种具有级联反应的多功能纳米系统可以有效抑制肿瘤生长并激活免疫反应。通过进一步与抗程序性死亡配体1（anti-PD-L1）检查点阻断疗法相结合，成功抑制了远处肿瘤生长和癌症转移。
