Walking Dead Tumor Cells for Targeted Drug Delivery Against Lung Metastasis of Triple-Negative Breast Cancer

Zitong Zhao; Lei Fang; Ping XiaoXiangshi SunLei ZhouXiaochen LiuJue WangGuanru WangHaiqiang CaoPengcheng ZhangYanyan JiangDangge WangYaping Li

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Walking Dead Tumor Cells for Targeted Drug Delivery Against Lung Metastasis of Triple-Negative Breast Cancer

机译：Walking Dead Tumor Cells for Targeted Drug Delivery Against Lung Metastasis of Triple-Negative Breast Cancer

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Lung metastasis is challenging in patients with triple-negative breast cancer(TNBC). Surgery is always not available due to the dissemination of metastaticfoci and most drugs are powerless because of poor retention at metastatic sites.TNBC cells generate an inflamed microenvironment and overexpress adhesivemolecules to promote invasion and colonization. Herein, “walking dead” TNBCcells are developed through conjugating anti-PD-1 (programmed death protein1 inhibitor) and doxorubicin (DOX)-loaded liposomes onto cell corpses for temporalchemo-immunotherapy against lung metastasis. The walking dead TNBCcells maintain plenary tumor antigens to conduct vaccination effects. Anti-PD-1antibodies are conjugated to cell corpses via reduction-activated linker, andDOX-loaded liposomes are attached by maleimide-thiol coupling. This anchorstrategy enables rapid release of anti-PD-1 upon reduction conditions while longlastingrelease of DOX at inflamed metastatic sites. The walking dead TNBCcells improve pulmonary accumulation and local retention of drugs, reprogramthe lung microenvironment through damage-associated molecular patterns(DAMPs) and PD-1 blockade, and prolong overall survival of lung metastatic 4T1and EMT6-bearing mice. Taking advantage of the walking dead TNBC cells forpulmonary preferred delivery of chemotherapeutics and checkpoint inhibitors,this study suggests an alternative treatment option of chemo-immunotherapy toaugment the efficacy against lung metastasis.

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《Advanced Materials》 |2022年第33期|2205462.1-2205462.13|共13页
作者
Zitong Zhao; Lei Fang; Ping XiaoXiangshi SunLei ZhouXiaochen LiuJue WangGuanru WangHaiqiang CaoPengcheng ZhangYanyan JiangDangge WangYaping Li;
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State Key Laboratory of Drug Research & Center of PharmaceuticsShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203, China, Shangdong Laboratory of Yantai Drug DiscoveryBohai Rim Advanced Research Institute for Drug DiscoveryShan;

State Key Laboratory of Drug Research & Center of PharmaceuticsShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203, China, Yantai Key Laboratory of Nanomedicine & Advanced PreparationsYantai Institute of Materia MedicaShandong 2;

School of PharmacyFudan UniversityShanghai 201203, ChinaState Key Laboratory of Drug Research & Center of PharmaceuticsShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203, China;

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正文语种英语
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chemo-immunotherapy; drug delivery; metastasis; PD-1 blockade; triplenegative breast cancer;

Walking Dead Tumor Cells for Targeted Drug Delivery Against Lung Metastasis of Triple-Negative Breast Cancer

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