通过使用凝胶状凝聚微滴外源性递送TRAIL抑制结肠癌复发
Inhibition of Colon Cancer Recurrence via Exogenous TRAIL Delivery Using Gel-like Coacervate Microdroplets.
作者信息
Kim Sungjun, Jwa Yerim, Hong Jiyeon, Kim Kyobum
机构信息
Department of Chemical & Biochemical Engineering, Dongguk University, 30, Pildong-ro 1-gil, Jung-gu, Seoul 22012, Korea.
出版信息
Gels. 2022 Jul 8;8(7):427. doi: 10.3390/gels8070427.
Colon cancer (CC) belongs to the three major malignancies with a high recurrence rate. Therefore, a novel drug delivery system that can prevent CC recurrence while minimizing side effects is needed. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) has recently been spotlighted as a protein drug that can induce apoptosis of cancer cells specifically. However, its short in vivo half-life is still a challenge to overcome. Hence, in this study, a gel-like mPEGylated coacervate (mPEG-Coa) delivery platform was developed through electrostatic interaction of mPEG-poly(ethylene arginylaspartate diglyceride) (mPEG-PEAD) and heparin for effective protection of cargo TRAIL, subsequently preserving its bioactivity. mPEG-Coa could protect cargo TRAIL against protease. Sustained release was observed for a long-term (14 days). In addition, recurrence of HCT-116 cells was suppressed when cells were treated with TRAIL-loaded mPEG-Coa for 7 days through long-term continuous supply of active TRAIL, whereas re-proliferation occurred in the bolus TRAIL-treated group. Taken together, these results suggest that our gel-like mPEG-Coa could be utilized as a functional delivery platform to suppress CC recurrence by exogenously supplying TRAIL for a long time with a single administration.
结肠癌(CC)是复发率较高的三大恶性肿瘤之一。因此,需要一种能够预防CC复发同时将副作用降至最低的新型药物递送系统。肿瘤坏死因子相关凋亡诱导配体(TRAIL)最近作为一种能够特异性诱导癌细胞凋亡的蛋白质药物受到关注。然而,其在体内的半衰期较短仍是一个需要克服的挑战。因此,在本研究中,通过mPEG-聚(乙烯基精氨酰天冬氨酸二甘油酯)(mPEG-PEAD)与肝素的静电相互作用,开发了一种凝胶状的聚乙二醇化凝聚层(mPEG-Coa)递送平台,以有效保护所载的TRAIL,进而保留其生物活性。mPEG-Coa可以保护所载的TRAIL免受蛋白酶的作用。观察到其具有长期(14天)的持续释放。此外,当用负载TRAIL的mPEG-Coa处理细胞7天时,通过长期持续供应活性TRAIL,HCT-116细胞的复发受到抑制,而在单次注射TRAIL处理组中出现了重新增殖。综上所述,这些结果表明,我们的凝胶状mPEG-Coa可以作为一种功能性递送平台,通过单次给药长期外源性供应TRAIL来抑制CC复发。
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