B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC
Abstract Background The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therap...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-02078-9 |
| _version_ | 1827708564167196672 |
|---|---|
| author | Bing Chen Kaifan Zheng Shubin Fang Kangping Huang Chengchao Chu Junyang Zhuang Jin Lin Shaoguang Li Hong Yao Ailin Liu Gang Liu Jizhen Lin Xinhua Lin |
| author_facet | Bing Chen Kaifan Zheng Shubin Fang Kangping Huang Chengchao Chu Junyang Zhuang Jin Lin Shaoguang Li Hong Yao Ailin Liu Gang Liu Jizhen Lin Xinhua Lin |
| author_sort | Bing Chen |
| collection | DOAJ |
| description | Abstract Background The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). Results In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. Conclusion This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC. |
| first_indexed | 2024-03-10T17:07:21Z |
| format | Article |
| id | doaj.art-e4d1b766ea6144b1b8c0d604dd2b1ef1 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-10T17:07:21Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-e4d1b766ea6144b1b8c0d604dd2b1ef12023-11-20T10:47:55ZengBMCJournal of Nanobiotechnology1477-31552023-10-0121111910.1186/s12951-023-02078-9B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLCBing Chen0Kaifan Zheng1Shubin Fang2Kangping Huang3Chengchao Chu4Junyang Zhuang5Jin Lin6Shaoguang Li7Hong Yao8Ailin Liu9Gang Liu10Jizhen Lin11Xinhua Lin12Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical UniversityKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical UniversityThe Cancer Center, Union Hospital, Fujian Medical UniversityKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical UniversityState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen UniversityKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical UniversityDepartment of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical UniversityKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical UniversityKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical UniversityKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical UniversityState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen UniversityThe Cancer Center, Union Hospital, Fujian Medical UniversityKey Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical UniversityAbstract Background The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). Results In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. Conclusion This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.https://doi.org/10.1186/s12951-023-02078-9B7H3/CD276Gold nanocageDoxorubicin conjugatesChemo-photothermal therapyNSCLC |
| spellingShingle | Bing Chen Kaifan Zheng Shubin Fang Kangping Huang Chengchao Chu Junyang Zhuang Jin Lin Shaoguang Li Hong Yao Ailin Liu Gang Liu Jizhen Lin Xinhua Lin B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC Journal of Nanobiotechnology B7H3/CD276 Gold nanocage Doxorubicin conjugates Chemo-photothermal therapy NSCLC |
| title | B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC |
| title_full | B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC |
| title_fullStr | B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC |
| title_full_unstemmed | B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC |
| title_short | B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC |
| title_sort | b7h3 targeting gold nanocage ph sensitive conjugates for precise and synergistic chemo photothermal therapy against nsclc |
| topic | B7H3/CD276 Gold nanocage Doxorubicin conjugates Chemo-photothermal therapy NSCLC |
| url | https://doi.org/10.1186/s12951-023-02078-9 |
| work_keys_str_mv | AT bingchen b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT kaifanzheng b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT shubinfang b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT kangpinghuang b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT chengchaochu b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT junyangzhuang b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT jinlin b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT shaoguangli b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT hongyao b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT ailinliu b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT gangliu b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT jizhenlin b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc AT xinhualin b7h3targetinggoldnanocagephsensitiveconjugatesforpreciseandsynergisticchemophotothermaltherapyagainstnsclc |