Enabling tumor-specific drug delivery by targeting the Warburg effect of cancer

Zhang, Jian; Pan, Tony; Lee, Jimmy; Goldberg, Sanja; King, Sarah Ann; Tang, Erting; Hu, Yifei; Chen, Lifeng; Hoover, Alex; Zhu, Linyong; Eng, Oliver S.; Dekel, Benjamin; Huang, Jun; Wu, Xiaoyang

doi:10.6082/21mch-9ma98

Published January 13, 2025 | Version v1

Journal article Open

Enabling tumor-specific drug delivery by targeting the Warburg effect of cancer

1. University of Chicago
2. Sheba Medical Center
3. East China University of Science & Technology
4. University of California, Irvine

Metabolic reprogramming of tumor cells is an emerging hallmark of cancer. Among all the changes in cancer metabolism, increased glucose uptake and the accumulation of lactate under normoxic conditions (the "Warburg effect") is a common feature of cancer cells. In this study, we develop a lactate-responsive drug delivery platform by targeting the Warburg effect. We design and test a gold/mesoporous silica Janus nanoparticle system as a gated drug carrier, in which the gold particles are functionalized with lactate oxidase and the silica particles are capped with α-cyclodextrin through surface arylboronate modification. In the presence of lactate, the lactate oxidase generates hydrogen peroxide, which induces the self-immolation reaction of arylboronate, leading to uncapping and drug release. Our results demonstrate greatly improved drug delivery specificity and therapeutic efficacy with this platform for the treatment of different cancers. Our findings present an effective approach for drug delivery by metabolic targeting of tumors.

Data availability

scRNA-seq data have been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table. Microscopy data reported in this paper will be shared by the lead contact upon request.

This paper does not report original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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