Cancer cell-targeted cisplatin prodrug delivery in vivo via metabolic labeling and bioorthogonal click reaction

Xun Liu, Fan Wu, Kaimin Cai, Ziyin Zhao, Zhimin Zhang, Yongbing Chen, Yong Liu, Jianjun Cheng, Lichen Yin

Research output: Contribution to journalArticlepeer-review

Abstract

The discrepancy of surface receptors on cancerous and non-cancerous cells has been regarded as the mainstay of cancer-Targeted therapy. However, due to the heterogeneity of tumor cells and the insufficient levels of receptors on the tumor cell surface, the success of cancer cell-Targeted therapies is largely limited. Histone deacetylase/cathepsin l-responsive acetylated azidomannose (DCL-AAM) was previously developed to effectively and selectively label cancer cell surfaces with reactive azido groups via sugar metabolism. Herein, the labeling kinetics and generality of DCL-AAM were systematically investigated in varieties of tumor cells in vitro and in SKOV3 xenograft tumors in vivo. Based on this, dibenzocyclooctyne-cisplatin (DBCO-Pt) prodrug was developed, and DCL-AAM-mediated metabolic labeling of SKOV3 cells enhanced the tumor accumulation of DBCO-Pt ∼2 fold via bioorthogonal click chemistry, potentiating the anti-Tumor efficacy of cisplatin yet alleviating the systemic toxicity. This work, therefore, provides the experimental and theoretical support for the future design of sugar metabolism-based targeted delivery systems and may provide a promising candidate for the treatment of cancers lacking appropriate biomarkers. This journal is

Original languageEnglish (US)
Pages (from-to)1301-1312
Number of pages12
JournalBiomaterials Science
Volume9
Issue number4
Early online dateDec 22 2020
DOIs
StatePublished - Feb 21 2021

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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