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Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma

التفاصيل البيبلوغرافية
العنوان: Co-administration of combretastatin A4 nanoparticles and anti-PD-L1 for synergistic therapy of hepatocellular carcinoma
المؤلفون: Bonan Zhao, Zhipeng Dong, Weixing Liu, Fangning Lou, Qiyan Wang, Hao Hong, Yue Wang
المصدر: Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-18 (2021)
بيانات النشر: BMC, 2021.
سنة النشر: 2021
المجموعة: LCC:Biotechnology
LCC:Medical technology
مصطلحات موضوعية: Combretastatin A4(CA4), Nanoparticles, Anti-PD-L1(aPD-L1), Synergistic therapy, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
الوصف: 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
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1477-3155
Relation: https://doaj.org/toc/1477-3155
DOI: 10.1186/s12951-021-00865-w
URL الوصول: https://doaj.org/article/3088622202054134b5607d616acd84e2
رقم الأكسشن: edsdoj.3088622202054134b5607d616acd84e2
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14773155
DOI:10.1186/s12951-021-00865-w