Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy

Jianzhi Zhu, Zhicong Li, Changchang Zhang, Lizhou Lin, Shoupeng Cao, Hailong Che, Xiangyang Shi (Corresponding author), Han Wang (Corresponding author), Jan C.M. van Hest (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
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Abstract

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 O2 from endogenous H2O2 to ameliorate the hypoxic and therefore poor-acoustic tumor environment. The generated O2 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.

Original languageEnglish
Pages (from-to)8048-8060
Number of pages13
JournalTheranostics
Volume9
Issue number26
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Catalase
  • Chemotherapy
  • PH-sensitive PEGylation
  • Polymer shell
  • Ultrasound-guided focused ultrasound ablation

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