肿瘤靶向和 GSH 刺激响应α-乳白蛋白纳米管联合输送多柔比星和 siRNA 用于癌症治疗

IF 5.2 Q1 FOOD SCIENCE & TECHNOLOGY Journal of Future Foods Pub Date : 2023-12-14 DOI:10.1016/j.jfutfo.2023.11.002
Guohua Hou , Di Wu , Xing Li , Bin Liu
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引用次数: 0

摘要

α-乳白蛋白(α-lac)是一种来源于食物的天然蛋白质,具有很高的生物相容性,可作为小生物活性分子或 RNA 的递送系统。然而,由于缺乏对肿瘤等理想组织的靶向性,其作为递送系统的临床应用潜力受到很大限制。本文通过α-漆水解肽的自组装,制备了一种纳米管(NT)递送系统/纳米载体。在装载抗肿瘤药物多柔比星(Dox)和 siRNA 的纳米管中,纳米管与 tLyp-1 多肽共轭,以特异性靶向存在于 MDA-MB-231 癌细胞膜上的神经纤蛋白 1 受体。在装载和靶向修饰过程中,NTs 的微观形态未受影响。此外,tLyp-1/NTs/Dox/siRNA 纳米载体在磷酸盐缓冲盐水中保存 7 天后,其大小和 zeta 电位均未发生明显变化,这表明其具有出色的稳定性。此外,经 tLyp-1 改性后,NTs 对 MDA-MB-231 乳腺癌细胞的细胞摄取效率和肿瘤蓄积效应都得到了显著改善。经 tLyp-1/NTs/Dox/siRNA (5 μg/mL Dox)处理后,MDA-MB-231 细胞在体外的相对存活率降低了 70.1%。最后,在对 MDA-MB-231 肿瘤小鼠进行抗癌治疗时,tLyp-1/NTs 中的 Dox 和 siRNA 发挥了协同抗癌作用。这些研究结果表明,食物来源的蛋白质α-lac纳米载体可用于生物活性分子和RNA的联合递送,实现协同高效的治疗效果。
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Tumor targeted and GSH stimuli-response α‑lactalbumin nanotubes co-delivering doxorubicin and siRNA for cancer therapy

α-Lactalbumin (α-lac), a natural food-sourced protein, exhibits high biocompatibility as delivery systems for small bioactive molecules or RNA. However, their potential clinical application as a delivery system is greatly limited due to the lack of targeting to desired tissues, such as tumors. Here, a delivery system/nanocarrier of nanotube (NT) was fabricated by the self-assembly of peptides hydrolyzed from α-lac. Among the loading of anti-tumor agents of doxorubicin (Dox) and siRNA, NTs were conjugated with the tLyp-1 peptide to specifically target the neuropilin 1 receptor, which exists on the membrane of MDA-MB-231 cancer cells. The micromorphology of NTs was not affected during the processes of loading and targeting modification. Additionally, no significant changes in the size and zeta potential of the tLyp-1/NTs/Dox/siRNA nanocarrier were observed when stored in phosphate buffered saline for 7 days, indicating outstanding stability. Moreover, both the cellular uptake efficiency and tumor accumulation effects of NTs on MDA-MB-231 breast cancer cells were significantly improved after modification with tLyp-1. The relative viability of MDA-MB-231 cells was decreased by 70.1% in vitro after treatment with tLyp-1/NTs/Dox/siRNA (5 μg/mL Dox). Finally, a synergistic anticancer effect of Dox and siRNA co-loaded in tLyp-1/NTs was achieved in the anticancer treatment of MDA-MB-231 tumor-bearing mice. These findings indicate that food-sourced protein α‑lac nanocarriers could be used for the co-delivery of bioactive molecules and RNA, achieving synergistic and efficient therapeutic effects.

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