Nanoparticles Coated with Neutrophil Membranes Can Effectively Treat Cancer Metastasis

TLDR

Dissemination, seeding, and colonization of circulating tumor cells (CTCs) drive distant metastasis, and colonization in the pre‑metastatic niche is a key early step. The study aimed to develop a neutrophil‑mimicking nanoparticle (NM‑NP) that targets CTCs and the metastatic niche. NM‑NPs were created by coating PLGA nanoparticles with neutrophil membranes, preserving membrane‑associated proteins that confer CTC‑binding and niche‑homing activity. NM‑NPs, especially when loaded with carfilzomib, showed superior CTC capture, homing to the pre‑metastatic niche, and prevention of early metastasis compared to uncoated NPs.

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.