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Copper-Doped Nanoscale Covalent Organic Polymer for Augmented Photo/Chemodynamic Synergistic Therapy and Immunotherapy.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-05-11 , DOI: 10.1021/acs.bioconjchem.0c00209 Chunling Hu 1, 2 , Lihan Cai 1, 2 , Sainan Liu 1, 2 , Ying Liu 1 , Ying Zhou 1 , Maolin Pang 1, 2
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-05-11 , DOI: 10.1021/acs.bioconjchem.0c00209 Chunling Hu 1, 2 , Lihan Cai 1, 2 , Sainan Liu 1, 2 , Ying Liu 1 , Ying Zhou 1 , Maolin Pang 1, 2
Affiliation
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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, p-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 O2 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.
中文翻译：
铜掺杂纳米级共价有机聚合物，用于增强的光/化学动力学协同疗法和免疫疗法。
由于特定的肿瘤微环境（TME）和癌细胞的免疫抑制状态，常规的抗肿瘤疗法面临严峻的挑战，例如高复发率和转移率。本文中，基于乙酸铜p合成了Cu-PPT纳米粒子-苯二胺和5,10,15,20-四-（4-氨基苯基）卟啉首次通过氧化偶联反应，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）。聚合物纳米颗粒在650 nm和808 nm激光照射下表现出优异的光动力学和光热效应，光热转化效率分别为40.1％。封装的Cu（I）/ Cu（II）离子允许Cu-PPT与谷胱甘肽（GSH）过氧化物酶模拟，过氧化氢酶模拟和Fenton样活性一起调节TME。耗尽过表达的谷胱甘肽会降低抗氧化能力，产生O 2可以减轻缺氧以增强PDT，而PTT的高温可以促进·OH的产生。具有级联反应的多功能纳米系统可以抑制肿瘤生长并有效激活免疫反应。通过进一步与抗编程死亡配体1（anti-PD-L1）检查点封锁疗法结合，可以成功地抑制远处的肿瘤生长和癌症转移。
更新日期：2020-05-11
中文翻译：
铜掺杂纳米级共价有机聚合物，用于增强的光/化学动力学协同疗法和免疫疗法。
由于特定的肿瘤微环境（TME）和癌细胞的免疫抑制状态，常规的抗肿瘤疗法面临严峻的挑战，例如高复发率和转移率。本文中，基于乙酸铜p合成了Cu-PPT纳米粒子-苯二胺和5,10,15,20-四-（4-氨基苯基）卟啉首次通过氧化偶联反应，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）。聚合物纳米颗粒在650 nm和808 nm激光照射下表现出优异的光动力学和光热效应，光热转化效率分别为40.1％。封装的Cu（I）/ Cu（II）离子允许Cu-PPT与谷胱甘肽（GSH）过氧化物酶模拟，过氧化氢酶模拟和Fenton样活性一起调节TME。耗尽过表达的谷胱甘肽会降低抗氧化能力，产生O 2可以减轻缺氧以增强PDT，而PTT的高温可以促进·OH的产生。具有级联反应的多功能纳米系统可以抑制肿瘤生长并有效激活免疫反应。通过进一步与抗编程死亡配体1（anti-PD-L1）检查点封锁疗法结合，可以成功地抑制远处的肿瘤生长和癌症转移。
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