DataVXAdvanced SciencePaper
journal article·2026-03Open access

Pro‐ATO/Allicin Liposomes for Dual‐Pathway Targeting of p53‐Mutant Tumors

Xiaoling Xu, WeiYi Cheng, Menghang Yang, Li He, WeiYe Ren, JingQuan Chen, LiTing He, Dandan Bao, Zhihong Zhu, Lixin Wang, Qinghua Yao, Ji‐Gang Piao

Advanced Science· Volume 13· Issue 18
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Source abstract

Abstract

ABSTRACT Mutations in the tumor suppressor p53 disrupt DNA damage response (DDR) and drive therapeutic resistance in lung cancer. Although arsenic trioxide (ATO) can restore transcriptional activity of structural p53 mutants, its clinical application is limited by subtype selectivity and systemic toxicity. In parallel, p53 deficiency creates dependence on S/G2 checkpoints, rendering ATR a synthetic lethal target; however, allicin, a natural ATR inhibitor and hydrogen sulfide (H 2 S) donor, suffers from poor stability and bioavailability. Here, we developed a liposomal nanomedicine co‐delivering pro‐ATO (As 5+ ) and allicin (AsAcP@LP) to integrate mutant p53 reactivation with DDR‐targeted synthetic lethality. This formulation improves drug stability, pharmacokinetics, and tumor accumulation while masking allicin's odor. Upon tumor‐specific release, allicin‐mediated redox activation converts As 5+ to cytotoxic As 3+ , enabling selective p53 reactivation, concurrent ATR inhibition, and H 2 S‐amplified apoptosis. AsAcP@LP exhibits synergistic antitumor efficacy with favorable tolerability, providing a rational nanotherapeutic strategy for p53‐mutant cancers.
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Research context

Nanomaterials

OpenAlex topics: Retinoids in leukemia and cellular processes · Arsenic contamination and mitigation · Garlic and Onion Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Radiation Oncology Shanghai Pulmonary Hospital Tongji University School of Medicine Shanghai China

Zhejiang Provincial Key Laboratory of Diagnosis and Treatment of Thoracic Cancer Hangzhou Zhejiang China

School of Pharmaceutical Sciences The First Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou Zhejiang China

Department of Dermatology & Cosmetology The First Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou Zhejiang China

Department of Integrative Medicine Shanghai Pulmonary Hospital Tongji University School of Medicine Shanghai China

Department of Oncology The Second Affiliated Hospital of Zhejiang Chinese Medical University Xinhua Hospital of Zhejiang Province Hangzhou Zhejiang China

Key Laboratory for Research on the Pathogenesis of ‘Inflammation‐Cancer Transformation’ in Intestinal Diseases Hangzhou Zhejiang China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Zhejiang Province · Natural Science Foundation of Shanghai Municipality

References (40)

Show source-provided references
1. 10.1186/s12935-021-02396-810.1186/s12935-021-02396-8 ↗
2. 10.1016/j.tig.2022.02.01010.1016/j.tig.2022.02.010 ↗
3. 10.1073/pnas.211323311910.1073/pnas.2113233119 ↗
4. 10.1038/s41420-022-01190-310.1038/s41420-022-01190-3 ↗
5. 10.1002/path.510710.1002/path.5107 ↗
6. 10.1016/j.phymed.2021.15353410.1016/j.phymed.2021.153534 ↗
7. 10.1158/1538-7445.AM2025-405310.1158/1538-7445.AM2025-4053 ↗
8. 10.1158/1538-7445.AM2021-248710.1158/1538-7445.AM2021-2487 ↗
9. 10.1016/j.jmb.2017.03.03010.1016/j.jmb.2017.03.030 ↗
10. 10.1111/joim.2010610.1111/joim.20106 ↗
11. 10.1038/s41392-023-01347-110.1038/s41392-023-01347-1 ↗
12. 10.1038/s41586-022-05082-510.1038/s41586-022-05082-5 ↗
13. 10.1038/s41418-022-00989-y10.1038/s41418-022-00989-y ↗
14. 10.1038/s41568-022-00535-510.1038/s41568-022-00535-5 ↗
15. 10.1038/s41419-022-05408-110.1038/s41419-022-05408-1 ↗
16. 10.1038/s41418-022-00962-910.1038/s41418-022-00962-9 ↗
17. 10.1002/ijc.3319710.1002/ijc.33197 ↗
18. 10.1016/j.ccell.2020.11.01310.1016/j.ccell.2020.11.013 ↗
19. 10.1093/jmcb/mjab00710.1093/jmcb/mjab007 ↗
20. 10.1038/s41568-021-00337-110.1038/s41568-021-00337-1 ↗
21. 10.1016/j.ccell.2021.01.01210.1016/j.ccell.2021.01.012 ↗
22. 10.1016/j.radonc.2017.09.04310.1016/j.radonc.2017.09.043 ↗
23. 10.1038/s41573-022-00558-510.1038/s41573-022-00558-5 ↗
24. 10.1016/j.phrs.2022.10616210.1016/j.phrs.2022.106162 ↗
25. 10.1016/j.celrep.2020.10809610.1016/j.celrep.2020.108096 ↗
26. 10.1038/ncb334410.1038/ncb3344 ↗
27. 10.1182/blood‐2015‐05‐64487210.1182/blood‐2015‐05‐644872 ↗
28. 10.1038/onc.2010.62410.1038/onc.2010.624 ↗
29. 10.1021/tx960176810.1021/tx9601768 ↗
30. 10.3892/ol.2017.612910.3892/ol.2017.6129 ↗
31. 10.1590/S0100‐879X201000750000410.1590/S0100‐879X2010007500004 ↗
32. 10.1016/j.ntm.2025.10008210.1016/j.ntm.2025.100082 ↗
33. 10.1016/j.jconrel.2024.06.00510.1016/j.jconrel.2024.06.005 ↗
34. 10.1016/j.biomaterials.2014.11.01010.1016/j.biomaterials.2014.11.010 ↗
35. 10.1002/EXP.2023009010.1002/EXP.20230090 ↗
36. 10.2147/DMSO.S47241210.2147/DMSO.S472412 ↗
37. 10.1016/j.trsl.2024.03.00210.1016/j.trsl.2024.03.002 ↗
38. 10.1038/s41419-018-1128-210.1038/s41419-018-1128-2 ↗
39. 10.1038/s41467-022-34348-910.1038/s41467-022-34348-9 ↗
40. 10.1371/journal.pbio.100185610.1371/journal.pbio.1001856 ↗