期刊
THERANOSTICS
卷 9, 期 26, 页码 8048-8060出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.37054
关键词
Catalase; polymer shell; pH-sensitive PEGylation; ultrasound-guided focused ultrasound ablation; chemotherapy
资金
- Netherlands Ministry of Education, Culture and Science [024.001.035]
- National Natural Science Foundation of China [81761148028, 21773026, 81871400, 81671740]
- Grant of Shanghai Science and Technology Commission [18441905000, 17XD1424200]
- Shanghai Municipal Commission of Health [2017BR038]
- China Scholarship Council
Constructing nanosystems that synergistically combine therapeutic and diagnostic features is of great interest to the nanomedicine community but also remains a tremendous challenge. Methods: 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. Results: The PEGylated nCAT produced highly effectively O-2 from endogenous H2O2 to ameliorate the hypoxic and therefore poor-acoustic tumor environment. The generated O-2 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 in vivo circulation time over 48 h and on the other hand enabled PEG cleavage in the vicinity of cancer cells to facilitate cellular uptake. Conclusion: The developed PEGylated nCAT can therefore effectively combine US-guided FUS and chemotherapy and can be regarded as a highly promising theranostic platform.
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