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红细胞膜包覆的聚乳酸-羟基乙酸共聚物/三氧化二砷纳米粒的制备、表征及其抗肿瘤效果评价

Preparation and characterization of erythrocyte membrane cloaked PLGA/arsenic trioxide nanoparticles and evaluation of their anti-tumor effect.

作者信息

Su Jing, Liu Geyi, Lian Yumei, Kamal Zul, Que Xiao, Qiu Yujiao, Qiu Mingfeng

机构信息

School of Pharmacy, Shanghai Jiao Tong University 800, Dongchuan Road Shanghai 200240 China

Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal Dir (Upper) 18000 Khyber Pakhtunkhwa Pakistan.

出版信息

RSC Adv. 2018 Jun 1;8(36):20068-20076. doi: 10.1039/c8ra01417e. eCollection 2018 May 30.

Abstract

Arsenic trioxide (ATO) is used for acute promyelocytic leukemia (APL) that is resistant to all--retinoic acid, but its direct intravenous injection sometimes induces severe toxic side effects. Here, we developed a delivery system of red blood cell membrane (RBCM) cloaked poly (lactic--glycolic) acid (PLGA)-ATO nanoparticles (RPANs) to reduce the toxicity. PLGA was used to entrap the ATO, and the PLGA-ATO nanoparticles (PANs) were prepared by the emulsification method. Then RBCMs were employed to cloak the PANs using ultrasonication, to develop the RPANs delivery system. The prepared RPANs had a uniform size of around 233.6 nm with an obvious core-shell structure, as observed by TEM. The completeness of the membrane proteins was confirmed by SDS-PAGE and an release time of 65 h was determined for the RPANs. The RPANs also exhibited low cytotoxicity against the 293k kidney cell line (84.6% cell viability rate), which suggested that the ATO toxicity was reduced by RBCM cloaking. Moreover, the anti-tumor effects of the RPANs against the HL60 cell line were comparable to those of ATO solution. Our study demonstrated that the RPANs system has anti-tumor potential and could be developed into a safe and sustained release delivery system for ATO.

摘要

三氧化二砷(ATO)用于治疗对全反式维甲酸耐药的急性早幼粒细胞白血病(APL),但其直接静脉注射有时会引发严重的毒副作用。在此,我们开发了一种红细胞膜(RBCM)包覆的聚乳酸-乙醇酸共聚物(PLGA)-ATO纳米颗粒(RPANs)递送系统以降低毒性。PLGA用于包裹ATO,通过乳化法制备PLGA-ATO纳米颗粒(PANs)。然后利用超声处理使RBCM包裹PANs,从而开发出RPANs递送系统。通过透射电子显微镜观察,所制备的RPANs尺寸均匀,约为233.6 nm,具有明显的核壳结构。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)证实了膜蛋白的完整性,并测定了RPANs的释放时间为65小时。RPANs对293k肾细胞系也表现出低细胞毒性(细胞活力率为84.6%),这表明RBCM包裹降低了ATO的毒性。此外,RPANs对HL60细胞系的抗肿瘤作用与ATO溶液相当。我们的研究表明,RPANs系统具有抗肿瘤潜力,可开发成为一种安全的ATO缓释递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb04/9080777/efb4910715cc/c8ra01417e-f1.jpg

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