Zhu Jianzhi, Li Zhicong, Zhang Changchang, Lin Lizhou, Cao Shoupeng, Che Hailong, Shi Xiangyang, Wang Han, van Hest Jan C M
Bio-Organic Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands.
State Key Laboratory for Modification of Chemical Fiber and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
Theranostics. 2019 Oct 17;9(26):8048-8060. doi: 10.7150/thno.37054. eCollection 2019.
Constructing nanosystems that synergistically combine therapeutic and diagnostic features is of great interest to the nanomedicine community but also remains a tremendous challenge. In this work, we report novel catalytic nanoparticles composed of the enzyme catalase, encapsulated in a polymer shell and surface decorated with pH-sensitive poly(ethylene glycol) (PEGylated nCAT). These nanoparticles were used as a promoter for ultrasound (US)-guided focused ultrasound (FUS) ablation and hypoxia alleviation for application in Doxorubicin-based chemotherapy. The PEGylated nCAT produced highly effectively O from endogenous HO to ameliorate the hypoxic and therefore poor-acoustic tumor environment. The generated O was utilized as 1) a contrast agent for US imaging; 2) strengthening agent for FUS ablation and 3) normoxia inducer to enhance chemotherapeutic efficacy. The PEGylated nCAT exhibited favorable enzyme activity after long-term storage, and after exposure to proteolytic conditions and elevated temperatures. The pH-responsive PEGylation contributed on the one hand to an extended circulation time over 48 h and on the other hand enabled PEG cleavage in the vicinity of cancer cells to facilitate cellular uptake. The developed PEGylated nCAT can therefore effectively combine US-guided FUS and chemotherapy and can be regarded as a highly promising theranostic platform.
构建具有治疗和诊断协同功能的纳米系统是纳米医学领域的研究热点，但仍面临巨大挑战。在本研究中，我们报道了一种新型催化纳米颗粒，其由过氧化氢酶组成，包裹在聚合物壳中，并在表面修饰了pH敏感的聚乙二醇（聚乙二醇化nCAT）。这些纳米颗粒被用作超声（US）引导的聚焦超声（FUS）消融和缺氧缓解的促进剂，用于基于阿霉素的化疗。聚乙二醇化nCAT能高效地将内源性过氧化氢转化为氧气，改善缺氧及声学性能差的肿瘤环境。产生的氧气可作为：1）超声成像的造影剂；2）增强FUS消融的试剂；3）常氧诱导剂以提高化疗疗效。聚乙二醇化nCAT在长期储存后，以及在暴露于蛋白水解条件和高温后，仍表现出良好的酶活性。pH响应性聚乙二醇化一方面延长了循环时间超过48小时，另一方面使聚乙二醇在癌细胞附近裂解，促进细胞摄取。因此，所开发的聚乙二醇化nCAT可以有效地结合US引导的FUS和化疗，可被视为一个极具前景的诊疗平台。
