Light-activated multimodal nanoplatform for enhanced synergistic therapy of breast cancer

Abstract Breast cancer poses a significant health threat to women, as traditional chemotherapy often fails due to multidrug resistance and tumor adaptability. Moreover, the anti-apoptotic nature of these tumors limits the effectiveness of conventional treatments. Current therapeutic approaches, incl...

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Main Authors: Yu Liu, Senyi Gong, Waleed Aldahmash, Kamran Ashraf, Zhanxia Li, Imran Mahmood Khan, Sobia Niazi, Meijin Guo, Ali Mohsin
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-11165-w
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author Yu Liu
Senyi Gong
Waleed Aldahmash
Kamran Ashraf
Zhanxia Li
Imran Mahmood Khan
Sobia Niazi
Meijin Guo
Ali Mohsin
author_facet Yu Liu
Senyi Gong
Waleed Aldahmash
Kamran Ashraf
Zhanxia Li
Imran Mahmood Khan
Sobia Niazi
Meijin Guo
Ali Mohsin
author_sort Yu Liu
collection DOAJ
description Abstract Breast cancer poses a significant health threat to women, as traditional chemotherapy often fails due to multidrug resistance and tumor adaptability. Moreover, the anti-apoptotic nature of these tumors limits the effectiveness of conventional treatments. Current therapeutic approaches, including photodynamic therapy (PDT), face limitations in clinical application due to poor water solubility of photosensitizers and challenges in targeted delivery. This study aims to develop a multifunctional nanosystem that integrates PDT with gene therapy to enhance breast cancer treatment efficacy. Firstly, Fe3O4 hollow nanospheres were prepared to carry Ce6 drug to kill breast cancer cells via chemodynamic therapy and PDT, respectively. To overcome the drawback of poor water solubility of PDT, HA/G3139/Ce6@Fe3O4 nanosystem was synthesized, which combines the benefits of G3139 antisense oligonucleotides for gene therapy and hyaluronic acid for encapsulation and targeting CD44 receptor. The developed novel nanosystem exhibits excellent biocompatibility and pH responsiveness, significantly enhancing its cancer cell-killing capability under light exposure. When the therapeutic system enters cancer cells and decomposes in the acidic environment, it releases Ce6 and G3139. On one hand, the photosensitizer Ce6 generates cytotoxic ROS upon irradiation, killing cancer cells; on the other hand, G3139 binds to the anti-apoptotic gene BCL-2 in cancer cells, downregulating the protein and inhibiting tumor proliferation. The novel nanosystem demonstrates synergistic anti-cancer effects by combining PDT, gene therapy, and chemodynamic therapy, leading to enhanced apoptosis in breast cancer cells. In conclusion, this approach offers a promising strategy for more effective and targeted breast cancer treatment.
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spelling doaj-art-d2f6c3f824b54b05a8e03b6005dd4bb92025-08-20T03:04:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-11165-wLight-activated multimodal nanoplatform for enhanced synergistic therapy of breast cancerYu Liu0Senyi Gong1Waleed Aldahmash2Kamran Ashraf3Zhanxia Li4Imran Mahmood Khan5Sobia Niazi6Meijin Guo7Ali Mohsin8State Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyZoology Department, College of Science, King Saud UniversityState Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyDepartment of Respiratory Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo ChinaState Key Laboratory of Food Science and Technology, Jiangnan UniversityState Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyState Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyAbstract Breast cancer poses a significant health threat to women, as traditional chemotherapy often fails due to multidrug resistance and tumor adaptability. Moreover, the anti-apoptotic nature of these tumors limits the effectiveness of conventional treatments. Current therapeutic approaches, including photodynamic therapy (PDT), face limitations in clinical application due to poor water solubility of photosensitizers and challenges in targeted delivery. This study aims to develop a multifunctional nanosystem that integrates PDT with gene therapy to enhance breast cancer treatment efficacy. Firstly, Fe3O4 hollow nanospheres were prepared to carry Ce6 drug to kill breast cancer cells via chemodynamic therapy and PDT, respectively. To overcome the drawback of poor water solubility of PDT, HA/G3139/Ce6@Fe3O4 nanosystem was synthesized, which combines the benefits of G3139 antisense oligonucleotides for gene therapy and hyaluronic acid for encapsulation and targeting CD44 receptor. The developed novel nanosystem exhibits excellent biocompatibility and pH responsiveness, significantly enhancing its cancer cell-killing capability under light exposure. When the therapeutic system enters cancer cells and decomposes in the acidic environment, it releases Ce6 and G3139. On one hand, the photosensitizer Ce6 generates cytotoxic ROS upon irradiation, killing cancer cells; on the other hand, G3139 binds to the anti-apoptotic gene BCL-2 in cancer cells, downregulating the protein and inhibiting tumor proliferation. The novel nanosystem demonstrates synergistic anti-cancer effects by combining PDT, gene therapy, and chemodynamic therapy, leading to enhanced apoptosis in breast cancer cells. In conclusion, this approach offers a promising strategy for more effective and targeted breast cancer treatment.https://doi.org/10.1038/s41598-025-11165-wBreast cancerPhotodynamic therapyFe3O4 Hollow nanosphereGene therapyTarget anti-apoptotic
spellingShingle Yu Liu
Senyi Gong
Waleed Aldahmash
Kamran Ashraf
Zhanxia Li
Imran Mahmood Khan
Sobia Niazi
Meijin Guo
Ali Mohsin
Light-activated multimodal nanoplatform for enhanced synergistic therapy of breast cancer
Scientific Reports
Breast cancer
Photodynamic therapy
Fe3O4 Hollow nanosphere
Gene therapy
Target anti-apoptotic
title Light-activated multimodal nanoplatform for enhanced synergistic therapy of breast cancer
title_full Light-activated multimodal nanoplatform for enhanced synergistic therapy of breast cancer
title_fullStr Light-activated multimodal nanoplatform for enhanced synergistic therapy of breast cancer
title_full_unstemmed Light-activated multimodal nanoplatform for enhanced synergistic therapy of breast cancer
title_short Light-activated multimodal nanoplatform for enhanced synergistic therapy of breast cancer
title_sort light activated multimodal nanoplatform for enhanced synergistic therapy of breast cancer
topic Breast cancer
Photodynamic therapy
Fe3O4 Hollow nanosphere
Gene therapy
Target anti-apoptotic
url https://doi.org/10.1038/s41598-025-11165-w
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