Senescent tumor cell membrane-based "time engine" nanosystem amplifies endoplasmic reticulum targeting for metastasis blockade.

Authors

Jing Tao, Yuzhen Guo, Fengzhi Zhang, Jiahui Wu, Liyun Xing, Jinxia Kong, Lian Li, Zhou Zhou, Yuan Huang

Published in

Science advances. Volume 12. Issue 41. Pages eaeh0494. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

As an important component of biomimetic drug delivery systems, cell membrane-coated nanoparticles are widely used for subcellular delivery. However, the influence of cell membranes at different life cycles on subcellular delivery remains unexplored. Our previous study demonstrated that senescent tumor cell membrane-coated nanoparticles (SNP) displayed superior endoplasmic reticulum (ER) targeting efficiency in tumor cells. After inducing tumor cells into senescence, SNP showed greater accumulation in ER. Herein, we design a "time engine" nanosystem for amplified ER targeting: Firstly, ribociclib is encapsulated into SNP (R@SNP) to induce tumor cell senescence; then, SNP loaded with brefeldin A (B@SNP) is used to trigger ER stress. By sequential therapy, R@SNP disrupts the cytoskeleton of 4T1 tumor cells to eliminate ER-targeting barriers and remodels the tumor immune microenvironment; B@SNP boosts ER-targeting efficiency and triggers intense ER stress. Collectively, such time engine nanosystem achieves excellent ER accumulation and antimetastatic efficacy in 4T1 tumor-bearing mice, providing an innovative perspective for subcellular delivery and tumor treatment.

PMID:
42853939
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

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