Issue 4, 2021

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

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
07 Oct 2020
Accepted
22 Nov 2020
First published
27 Nov 2020

Biomater. Sci., 2021,9, 1301-1312

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

X. Liu, F. Wu, K. Cai, Z. Zhao, Z. Zhang, Y. Chen, Y. Liu, J. Cheng and L. Yin, Biomater. Sci., 2021, 9, 1301 DOI: 10.1039/D0BM01709D

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