Doxorubicin Detoxification in Healthy Organs Improves Tolerability to High Drug Doses for Enhanced Antitumor Therapy

Qi Jiang, Mengchun Chen, Xuewei Yang, Deli Zhuge, Qingqing Yin, Dongyan Tian, Li Li, Xufei Zhang, Wenbin Xu, Shuangshuang Liu, Fan Li, Cuiye Weng, Yijing Lin, Haonan Wang, Dapang Rao, Yiming Chen, Qiangjun Cai, Linzhi Yan, Ledan Wang, Fang WangXiaosheng Lu, Bin Wen, Yingzheng Zhao, Feng Zhang, Weiliang Xia, Haiyan Zhu, Yijie Chen

Research output: Contribution to journalArticlepeer-review


With its well-documented toxicity, the use of doxorubicin (Dox) for cancer treatment requires trade-offs between safety and effectiveness. This limited use of Dox also hinders its functionality as an immunogenic cell death inducer, thus impeding its usefulness for immunotherapeutic applications. Here, we develop a biomimetic pseudonucleus nanoparticle (BPN-KP) by enclosing GC-rich DNA within erythrocyte membrane modified with a peptide to selectively target healthy tissue. By localizing treatment to organs susceptible to Dox-mediated toxicity, BPN-KP acts as a decoy that prevents the drug from intercalating into the nuclei of healthy cells. This results in significantly increased tolerance to Dox, thereby enabling the delivery of high drug doses into tumor tissue without detectable toxicity. By lessening the leukodepletive effects normally associated with chemotherapy, dramatic immune activation within the tumor microenvironment was also observed after treatment. In three different murine tumor models, high-dose Dox with BPN-KP pretreatment resulted in significantly prolonged survival, particularly when combined with immune checkpoint blockade therapy. Overall, this study demonstrates how targeted detoxification using biomimetic nanotechnology can help to unlock the full potential of traditional chemotherapeutics.

Original languageEnglish (US)
Pages (from-to)7705-7720
Number of pages16
JournalACS Nano
Issue number8
StatePublished - Apr 25 2023
Externally publishedYes


  • cancer therapy
  • detoxification
  • doxorubicin
  • immunotherapy
  • toxicity

ASJC Scopus subject areas

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


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