Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapy

Abstract The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers. Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. Currently, approaches for restoration of...

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Main Authors: Menglei Zhang, Yuanyuan Gu, Fang Shen, Yingxin Gong, Zheng Gu, Keqin Hua, Guannan Zhou, Jingxin Ding
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Journal of Ovarian Research
Subjects:
Online Access:https://doi.org/10.1186/s13048-025-01672-9
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author Menglei Zhang
Yuanyuan Gu
Fang Shen
Yingxin Gong
Zheng Gu
Keqin Hua
Guannan Zhou
Jingxin Ding
author_facet Menglei Zhang
Yuanyuan Gu
Fang Shen
Yingxin Gong
Zheng Gu
Keqin Hua
Guannan Zhou
Jingxin Ding
author_sort Menglei Zhang
collection DOAJ
description Abstract The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers. Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. Currently, approaches for restoration of TP53 expression, including small molecules and DNA therapies, have yielded progressive success, but each has formidable drawbacks. Here, we introduced an endogenous nanoplatform to effectively deliver the TP53 protein. Briefly speaking, the endogenous TP53 proteins were fused by the Lamp2b and loaded into extracellular vesicles-based nanoparticles, which could markedly restore the TP53 expression in natural TP53-deficient ovarian cancer (OCs) and subsequently inhibit cell proliferation as well as induce cell apoptosis. Moreover, a well-known biotin streptavidin binding strategy was used to confer the nanoplatform targeting ability. Since mesothelin (MSLN) expressed highly in ovarian cancer, the anti-MSLN nanoplatform were engineered to deliver TP53 proteins to MSLN ovarian cancer and exert the anti-tumor ability. Our findings indicated that restoration of tumor suppressors by the targeting nanoplatform could be promising nanotechnology approaches for potential ovarian cancer treatment.
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institution DOAJ
issn 1757-2215
language English
publishDate 2025-05-01
publisher BMC
record_format Article
series Journal of Ovarian Research
spelling doaj-art-cfdb05ff254e45ef88c984448656daf92025-08-20T03:09:19ZengBMCJournal of Ovarian Research1757-22152025-05-0118111610.1186/s13048-025-01672-9Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapyMenglei Zhang0Yuanyuan Gu1Fang Shen2Yingxin Gong3Zheng Gu4Keqin Hua5Guannan Zhou6Jingxin Ding7Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan UniversityAbstract The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers. Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. Currently, approaches for restoration of TP53 expression, including small molecules and DNA therapies, have yielded progressive success, but each has formidable drawbacks. Here, we introduced an endogenous nanoplatform to effectively deliver the TP53 protein. Briefly speaking, the endogenous TP53 proteins were fused by the Lamp2b and loaded into extracellular vesicles-based nanoparticles, which could markedly restore the TP53 expression in natural TP53-deficient ovarian cancer (OCs) and subsequently inhibit cell proliferation as well as induce cell apoptosis. Moreover, a well-known biotin streptavidin binding strategy was used to confer the nanoplatform targeting ability. Since mesothelin (MSLN) expressed highly in ovarian cancer, the anti-MSLN nanoplatform were engineered to deliver TP53 proteins to MSLN ovarian cancer and exert the anti-tumor ability. Our findings indicated that restoration of tumor suppressors by the targeting nanoplatform could be promising nanotechnology approaches for potential ovarian cancer treatment.https://doi.org/10.1186/s13048-025-01672-9NanoplatformTP53Ovarian cancerTargetingEngineering
spellingShingle Menglei Zhang
Yuanyuan Gu
Fang Shen
Yingxin Gong
Zheng Gu
Keqin Hua
Guannan Zhou
Jingxin Ding
Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapy
Journal of Ovarian Research
Nanoplatform
TP53
Ovarian cancer
Targeting
Engineering
title Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapy
title_full Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapy
title_fullStr Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapy
title_full_unstemmed Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapy
title_short Restoration of TP53 strategy via specific nanoparticles for ovarian cancer therapy
title_sort restoration of tp53 strategy via specific nanoparticles for ovarian cancer therapy
topic Nanoplatform
TP53
Ovarian cancer
Targeting
Engineering
url https://doi.org/10.1186/s13048-025-01672-9
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AT yingxingong restorationoftp53strategyviaspecificnanoparticlesforovariancancertherapy
AT zhenggu restorationoftp53strategyviaspecificnanoparticlesforovariancancertherapy
AT keqinhua restorationoftp53strategyviaspecificnanoparticlesforovariancancertherapy
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