机构：[1]Department of Pharmacology, School of Basic Medical Sciences &Department of Pharmacy, Shanghai Pudong Hospital, Fudan University, Shanghai 200032, P. R. China.[2]Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China.[3]Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.[4]School of Pharmacy & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201203, P. R. China.[5]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China.[6]Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, United States.[7]Shanghai Engineering Research Center for Synthetic Immunology, Fudan University, Shanghai 200032, P. R. China.
Liposomes are versatile drug delivery systems in clinical use for cancer and many other diseases. Unfortunately, PEGylated liposomal doxorubicin (sLip/DOX) exhibits serious dose-limiting cutaneous toxicities, which are closely related to the extravascular accumulation of sLip/DOX in the dermis. No clinical interventions have been proposed for cutaneous toxicities due to the elusive transport pathways. Herein, we showed that the reciprocal interaction between liposomes and neutrophils played pivotal roles in liposome extravasation into the dermis. Neutrophils captured liposomes via the complement receptor 3 (CD11b/CD18) recognizing the fragment of complement component C3 (iC3b) deposited on the liposomal surface. Uptake of liposomes also activated neutrophils to induce CD11b upregulation and enhanced the ability of neutrophils to migrate outside the capillaries. Furthermore, inhibition of complement activation either by CRIg-L-FH (a C3b/iC3b targeted complement inhibitor) or blocking the phosphate negative charge in mPEG-DSPE could significantly reduce liposome uptake by neutrophils and alleviate the cutaneous accumulation of liposomes. These results validated the liposome extravasation pathway mediated by neutrophils and provided potential solutions to the devastating cutaneous toxicities occurring during sLip/DOX treatment.
基金：
This work was supported by the National Natural ScienceFund of China (82125035, 32330058, and 82273866) andShanghai Education Commission Major Project (2021-01-07-00-07-E00081).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2024]版：
无
最新[2023]版：
大类|1 区材料科学
小类|1 区化学：综合1 区物理化学1 区材料科学：综合1 区纳米科技
第一作者：
第一作者机构：[1]Department of Pharmacology, School of Basic Medical Sciences &Department of Pharmacy, Shanghai Pudong Hospital, Fudan University, Shanghai 200032, P. R. China.
通讯作者：
通讯机构：[1]Department of Pharmacology, School of Basic Medical Sciences &Department of Pharmacy, Shanghai Pudong Hospital, Fudan University, Shanghai 200032, P. R. China.[4]School of Pharmacy & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201203, P. R. China.[7]Shanghai Engineering Research Center for Synthetic Immunology, Fudan University, Shanghai 200032, P. R. China.
推荐引用方式(GB/T 7714)：
Ding Tianhao,Wang Yang,Meng Yanchun,et al.Reciprocal Interaction with Neutrophils Facilitates Cutaneous Accumulation of Liposomes[J].ACS Nano.2024,18(28):18769-18784.doi:10.1021/acsnano.4c06638.
APA：
Ding Tianhao,Wang Yang,Meng Yanchun,Wu Ercan,Shao Qianwen...&Zhan Changyou.(2024).Reciprocal Interaction with Neutrophils Facilitates Cutaneous Accumulation of Liposomes.ACS Nano,18,(28)
MLA：
Ding Tianhao,et al."Reciprocal Interaction with Neutrophils Facilitates Cutaneous Accumulation of Liposomes".ACS Nano 18..28(2024):18769-18784
材料科学