Homotypic cell membrane-camouflaged biomimetic PLGA nanoparticle loading triptolide for the treatment of hepatocellular carcinoma.

IF 6.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Drug Delivery Pub Date : 2024-12-01 Epub Date: 2024-06-01 DOI:10.1080/10717544.2024.2354687
Zhe Li, Jinshuai Lan, Ya Wu, Yue Ding, Tong Zhang
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Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at -21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.

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用于治疗肝细胞癌的同型细胞膜伪装仿生聚乳酸(PLGA)纳米粒子。
肝细胞癌(HCC)是全球癌症相关死亡的第四大原因。除了早期发现、早期诊断和早期手术外,尝试治疗 HCC 的新策略也迫在眉睫。雷公藤内酯(TPL)已被用于治疗 HCC。然而,其治疗窗口期窄、毒性大、水溶性差等特点限制了其临床应用。在这项研究中,我们开发了具有同源靶向特性的负载 TPL 的癌细胞膜伪装仿生 PLGA 纳米颗粒(TPL@mPLGA),用于治疗 HCC。成功制备的TPL@mPLGA粒径为195.5 ± 7.5 nm,zeta电位为-21.5 ± 0.2 mV,具有良好的稳定性。TPL@mPLGA的载药量(DL)为2.94%。在TPL@mPLGA上包覆Huh-7细胞膜后,发现天然Huh-7细胞膜蛋白被保留在TPL@mPLGA上,从而使TPL@mPLGA在肿瘤部位的蓄积能力增强,与TPL或TPL@PLGA相比,TPL@mPLGA具有更好的体外和体内抗肿瘤活性。TPL@mPLGA的抗肿瘤作用增强,TPL的毒性降低,可用于治疗HCC。
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来源期刊
Drug Delivery
Drug Delivery 医学-药学
CiteScore
11.80
自引率
5.00%
发文量
250
审稿时长
3.3 months
期刊介绍: Drug Delivery is an open access journal serving the academic and industrial communities with peer reviewed coverage of basic research, development, and application principles of drug delivery and targeting at molecular, cellular, and higher levels. Topics covered include all delivery systems including oral, pulmonary, nasal, parenteral and transdermal, and modes of entry such as controlled release systems; microcapsules, liposomes, vesicles, and macromolecular conjugates; antibody targeting; protein/peptide delivery; DNA, oligonucleotide and siRNA delivery. Papers on drug dosage forms and their optimization will not be considered unless they directly relate to the original drug delivery issues. Published articles present original research and critical reviews.
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