Albumin-based nanoparticles combined with photodynamic therapy enhance the antitumor activity of curcumin derivative C086

Albumin-based nanoparticles combined with photodynamic therapy enhance the antitumor activity of curcumin derivative C086
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白蛋白纳米粒子联合光动力疗法增强姜黄素衍生物C086的抗肿瘤活性

DOI:
10.1016/j.dyepig.2021.109258
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发表时间:
2021-05
期刊:
影响因子:
4.5
通讯作者:
Zhuo Chen
Zhuo Chen
中科院分区:
材料科学2区
文献类型:
--
作者:
Chen He;Lei Zhang;Whenzhen Liu;Yunmei Huang;Ping Hu;Tao Dai;Jianhua Xu;Zhuo Chen

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C086是姜黄素的衍生物,是一种新型的热休克蛋白90(Hsp90)抑制剂,具有比姜黄素更强的抗肿瘤活性。然而,C086较差的水溶性限制了其生物利用度和治疗效果。在这项研究中,我们旨在通过基于白蛋白的纳米粒(NPs)来改善C086的溶解性,从而提高其生物利用度。采用简单的自组装方法制备了C086载人血清白蛋白(C086@HSA)纳米粒。由此得到的平均直径为36 nm的C086@HSA纳米粒子,与光动力疗法相结合,对所有被研究的肿瘤细胞株都显示出显著的细胞毒活性,并且作用时间比纯C086更长。进一步研究了C086@HSA纳米粒子的抗肿瘤机制,结果表明,C086@HSA纳米粒子对人宫颈癌HeLa细胞的光动力治疗作用与其在蓝光(450 nm,5 mW/cm2)照射10min时发生的细胞凋亡和细胞周期阻滞于S和G2/M期有关。此外,利用强蓝光(80 mW/cm2)对C086@HSA纳米粒在4T1荷瘤小鼠模型中的体内抗肿瘤活性进行了评价,证实了C086@HSA纳米粒通过光动力疗法具有增强的抗肿瘤活性。综上所述,我们的工作提供了一个高效的基于白蛋白的纳米药物传递平台,以提高疏水性光敏剂的生物利用度和抗肿瘤生长的治疗效果。
C086, a derivative of curcumin, was previously identified as a novel heat shock protein 90 (Hsp90) inhibitor and was found to exhibit stronger anti-tumor activity than curcumin. However, the inferior water solubility of C086 limits both its bioavailability and therapeutic efficacy. In this study, we aimed to improve the solubility and consequently the bioavailability of C086 via the albumin-based nanoparticles (NPs). The C086-loaded human serum albumin (C086@HSA) NPs were fabricated by a simple self-assembly method. The resulting C086@HSA NPs with an average diameter size of 36 nm, combined with photodynamic therapy, showed significant cytotoxic activity against all tumor cell lines investigated along with longer duration of effect than pure C086. More investigation was carried on the anti-tumor mechanism of C086@HSA NPs, showing that its anti-tumor effect of photodynamic therapy (PDT) on human cervical carcinoma HeLa cells was associated with apoptosis and cell cycle arrest at the S and G2/M phase upon 10-min blue light illumination (450 nm, 5 mW/cm2). Furthermore, thein vivoantitumor activity of C086@HSA NPs was evaluated in 4T1 tumor-bearing mouse model using intense blue light (80 mW/cm2), confirming the enhanced antitumor activity of C086@HSA NPs through photodynamic therapy. Taken together, our work provides an efficient albumin-based nanoparticle drug delivery platform to improve the bioavailability and therapeutic efficacy of hydrophobic photosensitizers against tumor growth.
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