Ultrasound-Activated, Tumor-Specific in Situ Synthesis of a Chemotherapeutic Agent Using ZIF-8 Nanoreactors for Precision Cancer Therapy

Putry Yosefa Siboro, Van Khanh Thi Nguyen, Yang Bao Miao, Amit Kumar Sharma, Fwu Long Mi, Hsin Lung Chen, Kuan Hung Chen, Yu Tzu Yu, Yen Chang, Hsing Wen Sung

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

The in situ transformation of low-toxicity precursors into a chemotherapeutic agent at a tumor site to enhance the efficacy of its treatment has long been an elusive goal. In this work, a zinc-based zeolitic imidazolate framework that incorporates pharmaceutically acceptable precursors is prepared as a nanoreactor (NR) system for the localized synthesis of an antitumor drug. The as-prepared NRs are administered intratumorally in a tumor-bearing mouse model and then irradiated with ultrasound (US) to activate the chemical synthesis. The US promotes the penetration of the administered NRs into the tumor tissue to cover the lesion entirely, although some NRs leak into the surrounding normal tissue. Nevertheless, only the tumor tissue, where the H2O2concentration is high, is adequately exposed to the as-synthesized antitumor drug, which markedly impedes development of the tumor. No significant chemical synthesis is detected in the surrounding normal tissue, where the local H2O2concentration is negligible and the US irradiation is not directly applied. The as-proposed tumor-specific in situ synthesis of therapeutic molecules induces hardly any significant in vivo toxicity and, thus, is potentially a potent biocompatible approach to precision chemotherapy.

Original languageEnglish
Pages (from-to)12403-12414
Number of pages12
JournalACS Nano
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 23 2022

Keywords

  • in situ synthesis
  • precision chemotherapy
  • pyrimidine-based derivative
  • sonotherapy
  • therapeutic nanoreactor

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy

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