期刊
ACS NANO
卷 11, 期 2, 页码 1397-1411出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.6b06477
关键词
circulating tumor cells; premetastatic niche; metastasis prevention; drug delivery; neutrophil-mimicking nanoparticles
类别
资金
- National Natural Science Foundation of China [81673019, 81573382, 61227017]
- Shanghai Science and Technology Committee [15540723700]
- Shu Guang project - Shanghai Municipal Education Commission
- Shanghai Education Development Foundation [15SG14]
- National Major Scientific Research Program of China [2011CB910404, 2012CB966801]
- National Science Fund for Distinguished Young Scholars [61425006]
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 CTCand 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.
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