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pH-Responsive Nanoscale Covalent Organic Polymers as a Biodegradable Drug Carrier for Combined Photodynamic Chemotherapy of Cancer
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-04-12 00:00:00 , DOI: 10.1021/acsami.8b02080 Hairong Wang 1 , Wenwen Zhu 1 , Jingjing Liu 1 , Ziliang Dong 1 , Zhuang Liu 1
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-04-12 00:00:00 , DOI: 10.1021/acsami.8b02080 Hairong Wang 1 , Wenwen Zhu 1 , Jingjing Liu 1 , Ziliang Dong 1 , Zhuang Liu 1
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Covalent organic polymers (COPs) are a promising class of cross-linked polymeric networks and porous structures composed of covalent organic molecules that attract extensive attention. Despite increasing interest in applying COPs for applications in nanomedicine, the pH-sensitive COPs that are able to sensitively respond to the slightly acidic tumor microenvironment for tumor-specific drug delivery and therapy remain to be explored to our best knowledge. Herein, a new style of pH-responsive COPs were prepared using acryloyl meso-tetra(p-hydroxyphenyl) porphine (acryloyl-THPP) to react with 4,4′-trimethylene dipiperidine to form the pH-responsive cross-linked biodegradable β-amino esters (BAEs). Amine-modified poly(ethylene glycol) (PEG) was then introduced to terminate the reaction and form the PEG shell. The formulated pH-responsive THPP–BAE–PEG COPs can be utilized to encapsulate anticancer drug doxorubicin (DOX) due to their porous structure. Upon intravenous injection, such DOX-loaded COPs show a prolonged blood circulation as well as an efficient tumor accumulation. Along with the pH-triggered drug release for chemotherapy, the singlet oxygen produced by THPP under light exposure for photodynamic therapy would further endow us a combined treatment strategy, which offers synergistic antitumor effects in our in vivo tumor model experiments. Our study illustrates that COPs fabricated with tumor microenvironment responsive linkers may be a promising type of materials for applications in cancer nanomedicine.
中文翻译：
pH响应的纳米级共价有机聚合物作为可生物降解的药物联合癌症的光动力化学疗法的药物载体。
共价有机聚合物（COPs）是一类有前途的交联聚合物网络，由共价有机分子组成的多孔结构引起了广泛的关注。尽管对将COPs用于纳米药物的兴趣日益浓厚，但能够对微酸性肿瘤微环境做出敏感反应以进行肿瘤特异性药物递送和治疗的pH敏感COPs仍需我们所掌握的知识进行探索。在此，使用丙烯酰基内消旋-四（p-羟基苯基）卟啉（丙烯酰基-THPP）与4,4'-三亚甲基二哌啶反应形成pH响应的可交联的可生物降解的β-氨基酯（BAE）。然后引入胺改性的聚（乙二醇）（PEG）以终止反应并形成PEG壳。配制的pH响应性THPP–BAE–PEG COP由于其多孔结构，可用于封装抗癌药阿霉素（DOX）。静脉内注射后，此类DOX负载的COP表现出延长的血液循环以及有效的肿瘤蓄积。伴随着pH触发的化学药物释放，THPP在光动力疗法下曝光产生的单线态氧将进一步赋予我们一种联合治疗策略，该策略在我们的体内肿瘤模型实验中具有协同的抗肿瘤作用。
更新日期：2018-04-12
中文翻译：
pH响应的纳米级共价有机聚合物作为可生物降解的药物联合癌症的光动力化学疗法的药物载体。
共价有机聚合物（COPs）是一类有前途的交联聚合物网络，由共价有机分子组成的多孔结构引起了广泛的关注。尽管对将COPs用于纳米药物的兴趣日益浓厚，但能够对微酸性肿瘤微环境做出敏感反应以进行肿瘤特异性药物递送和治疗的pH敏感COPs仍需我们所掌握的知识进行探索。在此，使用丙烯酰基内消旋-四（p-羟基苯基）卟啉（丙烯酰基-THPP）与4,4'-三亚甲基二哌啶反应形成pH响应的可交联的可生物降解的β-氨基酯（BAE）。然后引入胺改性的聚（乙二醇）（PEG）以终止反应并形成PEG壳。配制的pH响应性THPP–BAE–PEG COP由于其多孔结构，可用于封装抗癌药阿霉素（DOX）。静脉内注射后，此类DOX负载的COP表现出延长的血液循环以及有效的肿瘤蓄积。伴随着pH触发的化学药物释放，THPP在光动力疗法下曝光产生的单线态氧将进一步赋予我们一种联合治疗策略，该策略在我们的体内肿瘤模型实验中具有协同的抗肿瘤作用。
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