title: Nanoparticles Coated with Neutrophil Membranes Can Effectively Treat Cancer Metastasis.
abstract: The dissemination, seeding, and colonization of circulating tumor cells (CTCs) serve as the root of distant metastasis. As a key step in the early stage of metastasis formation, colonization of CTCs in the (pre-)metastatic niche appears to be a valuable target. Evidence showed that inflammatory neutrophils possess both a CTC- and niche-targeting property by the intrinsic cell adhesion molecules on neutrophils. Inspired by this mechanism, we developed a nanosize neutrophil-mimicking drug delivery system (NM-NP) by coating neutrophils membranes on the surface of poly(latic-co-glycolic acid) nanoparticles (NPs). The membrane-associated protein cocktails on neutrophils membrane were mostly translocated to the surface of NM-NP via a nondisruptive approach, and the biobinding activity of neutrophils was highly preserved. Compared with uncoated NP, NM-NP exhibited enhanced cellular association in 4T1 cell models under shear flow in vitro, much higher CTC-capture efficiency in vivo, and improved homing to the premetastatic niche. Following loading with carfilzomib, a second generation of proteasome inhibitor, the NM-NP-based nanoformulation (NM-NP-CFZ) selectively depleted CTCs in the blood, prevented early metastasis and potentially inhibited the progress of already-formed metastasis. Our NP design can neutralize CTCs in the circulation and inhibit the formation of a metastatic niche.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , Lane 826, Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Kang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , Lane 826, Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University , 1954 Huashan Road, Shanghai 200030, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wei
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , Lane 826, Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , Lane 826, Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Yao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , Lane 826, Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Tianze
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine , 280 South Chongqing Road, Shanghai 200025, P.R. China.
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Song
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University , 1954 Huashan Road, Shanghai 200030, P.R. China.
authors.forename: Xunbin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine , 280 South Chongqing Road, Shanghai 200025, P.R. China.
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine , 280 South Chongqing Road, Shanghai 200025, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , Lane 826, Zhangheng Road, Shanghai 201203, P.R. China.
authors.forename: Jun
authors.identifier: 0000-0003-1330-9616
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000473:pathology; D009504:Neutrophils / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010316:Particle Size; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009842:Oligopeptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C524865:carfilzomib
keywords: circulating tumor cells; drug delivery; metastasis prevention; neutrophil-mimicking nanoparticles; premetastatic niche