Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma
Abstract Background According to data estimated by the WHO, primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of death around the world. Hepatocellular carcinoma (HCC) is one of the most common primary liver malignancies, so effective therapy is hi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-00865-w |
| _version_ | 1811185849997459456 |
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| author | Bonan Zhao Zhipeng Dong Weixing Liu Fangning Lou Qiyan Wang Hao Hong Yue Wang |
| author_facet | Bonan Zhao Zhipeng Dong Weixing Liu Fangning Lou Qiyan Wang Hao Hong Yue Wang |
| author_sort | Bonan Zhao |
| collection | DOAJ |
| description | Abstract Background According to data estimated by the WHO, primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of death around the world. Hepatocellular carcinoma (HCC) is one of the most common primary liver malignancies, so effective therapy is highly desired for HCC. Results In this study, the use of poly(l-Aspartic acid)-poly(ethylene glycol)/combretastatin A4 (CA4-NPs) was aimed to significantly disrupt new blood vessels in tumor tissues for targeted hepatic tumor therapy. Here, PEG-b-PAsp-g-CA4 showed significantly prolonged retention in plasma and tumor tissue. Most importantly, CA4-NPs were mainly distributed at the tumor site because of the triple target effects—enhanced permeability and retention (EPR) effect, acid-sensitive (pH = 5.5) effect to the tumor microenvironment (TME), and good selectivity of CA4 for central tumor blood vessel. Considering that CA4-NPs might induce severe hypoxic conditions resulting in high expression of HIF-1α in tumor tissues, which could induce the overexpression of PD-L1, herein we also used a programmed death-ligand 1 antibody (aPD-L1) to prevent immunosuppression. This way of complementary combination is able to achieve an ideal treatment effect in tumor site where CA4-NPs and aPD-L1 could respond to the inner area and peripheral area, respectively. As a result, a significant decrease in tumor volume and weight was observed in the combination group of CA4-NPs plus aPD-L1 compared with CA4-NPs or aPD-L1 monotherapy in subcutaneous Hepa1-6 hepatic tumor models. Conclusions We presented a new idea that co-administration of CA4-NPs and aPD-L1 possessed notable anti-tumor efficacy for HCC treatment. Graphic abstract |
| first_indexed | 2024-04-11T13:37:21Z |
| format | Article |
| id | doaj.art-3088622202054134b5607d616acd84e2 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T13:37:21Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-3088622202054134b5607d616acd84e22022-12-22T04:21:26ZengBMCJournal of Nanobiotechnology1477-31552021-05-0119111810.1186/s12951-021-00865-wCo-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinomaBonan Zhao0Zhipeng Dong1Weixing Liu2Fangning Lou3Qiyan Wang4Hao Hong5Yue Wang6Key Laboratory of Biomedical Functional Materials, School of Sciences, China Pharmaceutical UniversityKey Laboratory of Biomedical Functional Materials, School of Sciences, China Pharmaceutical UniversityKey Laboratory of Biomedical Functional Materials, School of Sciences, China Pharmaceutical UniversityKey Laboratory of Biomedical Functional Materials, School of Sciences, China Pharmaceutical UniversityKey Laboratory of Biomedical Functional Materials, School of Sciences, China Pharmaceutical UniversitySchool of Medicine, Nanjing UniversityKey Laboratory of Biomedical Functional Materials, School of Sciences, China Pharmaceutical UniversityAbstract Background According to data estimated by the WHO, primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of death around the world. Hepatocellular carcinoma (HCC) is one of the most common primary liver malignancies, so effective therapy is highly desired for HCC. Results In this study, the use of poly(l-Aspartic acid)-poly(ethylene glycol)/combretastatin A4 (CA4-NPs) was aimed to significantly disrupt new blood vessels in tumor tissues for targeted hepatic tumor therapy. Here, PEG-b-PAsp-g-CA4 showed significantly prolonged retention in plasma and tumor tissue. Most importantly, CA4-NPs were mainly distributed at the tumor site because of the triple target effects—enhanced permeability and retention (EPR) effect, acid-sensitive (pH = 5.5) effect to the tumor microenvironment (TME), and good selectivity of CA4 for central tumor blood vessel. Considering that CA4-NPs might induce severe hypoxic conditions resulting in high expression of HIF-1α in tumor tissues, which could induce the overexpression of PD-L1, herein we also used a programmed death-ligand 1 antibody (aPD-L1) to prevent immunosuppression. This way of complementary combination is able to achieve an ideal treatment effect in tumor site where CA4-NPs and aPD-L1 could respond to the inner area and peripheral area, respectively. As a result, a significant decrease in tumor volume and weight was observed in the combination group of CA4-NPs plus aPD-L1 compared with CA4-NPs or aPD-L1 monotherapy in subcutaneous Hepa1-6 hepatic tumor models. Conclusions We presented a new idea that co-administration of CA4-NPs and aPD-L1 possessed notable anti-tumor efficacy for HCC treatment. Graphic abstracthttps://doi.org/10.1186/s12951-021-00865-wCombretastatin A4(CA4)NanoparticlesAnti-PD-L1(aPD-L1)Synergistic therapy |
| spellingShingle | Bonan Zhao Zhipeng Dong Weixing Liu Fangning Lou Qiyan Wang Hao Hong Yue Wang Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma Journal of Nanobiotechnology Combretastatin A4(CA4) Nanoparticles Anti-PD-L1(aPD-L1) Synergistic therapy |
| title | Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma |
| title_full | Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma |
| title_fullStr | Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma |
| title_full_unstemmed | Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma |
| title_short | Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma |
| title_sort | co administration of combretastatin a4 nanoparticles and anti pd l1 for synergistic therapy of hepatocellular carcinoma |
| topic | Combretastatin A4(CA4) Nanoparticles Anti-PD-L1(aPD-L1) Synergistic therapy |
| url | https://doi.org/10.1186/s12951-021-00865-w |
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