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Engineering a nano-drug delivery system to regulate m6A modification and enhance immunotherapy in gastric cancer

Li, Zhengshuo, Zhang, Xiaoyue, Liu, Can, Wu, Yangge, Wen, Yuqing, Zheng, Run, Xu, Chenxiao, Tian, Junrui, Peng, Qiu, Zheng, Xiang, Wang, Jia, Yan, Qun, Wei, Lingyu, Ma, Jian·2025·Acta Biomaterialia
DOI 10.1016/j.actbio.2024.11.036
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Abstract

Cancer cell membrane-derived nanoparticle drug delivery system enables precise drug delivery to tumor tissues and is a new effective way to treat solid tumors. The aim of this study is to develop a safe and effective cancer cell membrane-derived nano-delivery system targeting gastric cancer. We previously reported that EPH receptor A2 (EphA2) is an important target for gastric cancer. RNA m6A methyltransferases METTL3 is upregulated in multiple cancers and promotes cancer development by increasing the expression of multiple oncogenes. We design a new nano-delivery system PLGA-STM-TAT: nanoparticles PLGA (poly lactic acid-hydroxyacetic acid) loaded with METTL3 inhibitor STM2457 and cell-penetrating peptide TAT, and then covered with gastric cancer cell membranes equipped with YSA peptides by means of click chemistry, which targeting EphA2. The nanoparticles are specifically enriched in gastric cancer tissues, significantly increased drug accumulation, and inhibited cancer cell proliferation by decreasing key oncogenes c-MYC and BRD4. During drug administration, we found that the expression of the immune checkpoint molecule PD-L1 was suppressed, and the anti-tumor immune effect was enhanced by the nano-delivery system in combination with anti-PD1. This cancer cell membrane-derived nano-delivery system provides a new biological strategy to treat gastric cancer through effective m6A modulation and EphA2 targeting. STATEMENT OF SIGNIFICANCE: M6A modifications have important biolog…

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Research works printed but not linked: 24

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Metadata

Authors
Li, Z., Zhang, X., Liu, C., Wu, Y., Wen, Y., Zheng, R., Xu, C., Tian, J., Peng, Q., Zheng, X., Wang, J., Yan, Q., Wei, L., & Ma, J.
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2025-01
Volume
191
Pages
412-427
ISSN
1742-7061
DOI
10.1016/j.actbio.2024.11.036
Cited by
24
References
0
Language
en
Update notices
erratum (2025-04-01)
Licence
Funders
  • Postdoctoral Science Foundation of Central South University (140050041)
  • Natural Science Foundation of Hunan Province (2024JJ6551)
  • Education Department of Henan Province (23A0016)
  • China Postdoctoral Science Foundation (2024M753677)
  • National Natural Science Foundation of China (82060042, 82460464, 32000665, 82101907, 82073261)
  • Science and Technology Program of Hunan Province

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