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Peer-reviewedCC BYScience Advances

Senescent tumor cell membrane–based “time engine” nanosystem amplifies endoplasmic reticulum targeting for metastasis blockade

  • Jing Tao1
  • Yuzhen Guo1
  • Fengzhi Zhang1
  • Jiahui Wu1
  • Liyun Xing1
  • Jinxia Kong1
  • Lian Li1
  • Zhou Zhou1
  • Yuan Huang1
  1. 1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
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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.

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Cite

BibTeXRIS
BibTeX
@article{tao2026senescent,
  title = {{Senescent tumor cell membrane–based “time engine” nanosystem amplifies endoplasmic reticulum targeting for metastasis blockade}},
  author = {Jing Tao and Yuzhen Guo and Fengzhi Zhang and Jiahui Wu and Liyun Xing and Jinxia Kong and Lian Li and Zhou Zhou and Yuan Huang},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh0494},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh0494},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Senescent tumor cell membrane–based “time engine” nanosystem amplifies endoplasmic reticulum targeting for metastasis blockade
AU  - Jing Tao
AU  - Yuzhen Guo
AU  - Fengzhi Zhang
AU  - Jiahui Wu
AU  - Liyun Xing
AU  - Jinxia Kong
AU  - Lian Li
AU  - Zhou Zhou
AU  - Yuan Huang
PY  - 2026
DA  - 2026/10/09
JO  - Science Advances
DO  - 10.1126/sciadv.aeh0494
UR  - https://www.science.org/doi/10.1126/sciadv.aeh0494
AB  - 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.
SN  - 2375-2548
ER  -