DataVXACS NanoPaper
journal article·2023-04-25

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 Wang, Xiaosheng Lu, Bin Wen, Yingzheng Zhao, Feng Zhang, Weiliang Xia, Haiyan Zhu, Yijie Chen

ACS Nano· Volume 17· Issue 8
Publisher page
Source abstract

Abstract

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.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Nanoplatforms for cancer theranostics · Advanced biosensing and bioanalysis techniques · Nanoparticle-Based Drug Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China

International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu 322000, China

Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China

Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo 315302, China

Department of Pharmaceutics, School of Pharmaceutical Sciences of Wenzhou Medical University, Wenzhou 325035, China

Wenzhou Medical University, Wenzhou 325035, China

State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China

The National Engineering Research Center for Bioengineering Drugs and the Technologies, The Institute of Translational Medicine, Nanchang University, Nanchang 330031, China

Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200092, China

Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China

Funding

Wenzhou Municipal Science and Technology Bureau · National Natural Science Foundation of China · Natural Science Foundation of Zhejiang Province · Zhejiang Province

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