Sustained release of therapeutic gene by injectable hydrogel for hepatocellular carcinoma

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2023-06-26 DOI:10.1016/j.ijpx.2023.100195
Shuangta Xu , Jianya Cai , Hongwei Cheng , Wei Wang
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Abstract

Gene therapy has shown remarkable effectiveness in the management of disease like cancer and inflammation as a revolutionary therapeutic. Nonetheless, therapeutic drug target discovery, efficient gene delivery, and gene delivery vehicles continue to be significant obstacles. Due to their effective gene transport capabilities and low immunogenicity, supramolecular polymers have garnered significant interest. Herein, ABHD5 is identified as a potential therapeutic target since it is dysregulated in hepatocellular carcinoma (HCC). Interestingly, the downregulation of ABHD5 could induce programmed death-ligand 1 (PD-L1) expression in liver cancer, which may contribute to the immunosuppression. To overcome the immunosuppression caused by PD-L1, an injectable hydrogel is designed to achieve efficient abhydrolase domain containing 5 (ABHD5) gene delivery via the host-guest interaction with branched polyethyleneimine-g-poly (ethylene glycol), poly (ethylene oxide) and poly (propylene oxide) block copolymers and α-CD (PPA/CD), demonstrating the capability for sustained gene release. The co-assembly hydrogel demonstrates good biocompatibility and enhanced gene transfection efficiency, efficiently triggering tumor cell apoptosis. Overall, the results of this study suggest that ABHD5 is a potential therapeutic target, and that a host-guest-based supramolecular hydrogel could serve as a promising platform for the inhibition of HCC.

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可注射水凝胶缓释肝细胞癌治疗基因
基因疗法作为一种革命性的治疗方法,在癌症和炎症等疾病的治疗中显示出显著的有效性。尽管如此,治疗药物靶点的发现、有效的基因递送和基因递送载体仍然是重大障碍。超分子聚合物由于其有效的基因转运能力和低免疫原性,引起了人们的极大兴趣。在此,ABHD5被确定为潜在的治疗靶点,因为它在肝细胞癌(HCC)中失调。有趣的是,在癌症中,ABHD5的下调可能诱导程序性死亡配体1(PD-L1)的表达,这可能导致免疫抑制。为了克服PD-L1引起的免疫抑制,设计了一种可注射水凝胶,通过与支链聚乙烯亚胺-g-聚(乙二醇)、聚(环氧乙烷)和聚(环氧丙烷)嵌段共聚物以及α-CD(PPA/CD)的主客体相互作用,实现高效的含去水解酶结构域5(ABHD5)基因递送,证明了基因持续释放的能力。该共组装水凝胶表现出良好的生物相容性和增强的基因转染效率,有效地触发肿瘤细胞凋亡。总的来说,这项研究的结果表明,ABHD5是一个潜在的治疗靶点,并且基于宿主-客体的超分子水凝胶可以作为抑制HCC的一个有前途的平台。
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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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