含有多肽的工程细胞外囊泡用于靶向输送多柔比星,以对抗表皮生长因子受体阳性肿瘤。

IF 3.8 3区 医学 Q2 ONCOLOGY Oncology reports Pub Date : 2024-11-01 Epub Date: 2024-09-27 DOI:10.3892/or.2024.8813
Yuqing Yang, Fang Wang, Yuqin Li, Ruxi Chen, Xiangyu Wang, Jiahong Chen, Xi Lin, Haipeng Zhang, Youwei Huang, Rui Wang
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引用次数: 0

摘要

缺乏有效的肿瘤特异性给药系统仍然是使用细胞毒性药物进行化疗的一个尚未解决的临床难题。由于细胞外囊泡(EVs)具有良好的生物分布性、生物相容性和低免疫原性,最近研究人员对其作为高效给药平台的潜力进行了研究。本研究开发了负载多柔比星的GE11肽修饰EVs(GE11-EVs)配方(Dox-GE11-EVs),用于靶向表皮生长因子受体(EGFR)阳性肿瘤细胞。研究结果表明,与未经修饰的EVs相比,GE11-EVs对表皮生长因子受体阳性肿瘤细胞具有高效的靶向性和药物输送能力。此外,与Dox-EVs和游离Dox处理相比,用Dox-GE11-EVs处理表皮生长因子受体阳性肿瘤细胞可显著抑制细胞增殖并增加细胞凋亡。此外,还观察到游离 Dox 或 Dox-EVs 对正常细胞具有高度的细胞毒性,而 Dox-GE11-EVs 对正常细胞活力的影响有限。综上所述,本研究结果表明,与传统的肿瘤疗法相比,工程化的Dox-GE11-EVs能更准确地治疗表皮生长因子受体阳性肿瘤,而且安全性更高。
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Engineered extracellular vesicles with polypeptide for targeted delivery of doxorubicin against EGFR‑positive tumors.

Lack of effective tumor‑specific delivery systems remains an unmet clinical challenge for the employment of chemotherapy using cytotoxic drugs. Extracellular vesicles (EVs) have recently been investigated for their potential as an efficient drug‑delivery platform, due to their good biodistribution, biocompatibility and low immunogenicity. In the present study, the formulation of GE11 peptide‑modified EVs (GE11‑EVs) loaded with doxorubicin (Dox‑GE11‑EVs), was developed to target epidermal growth factor receptor (EGFR)‑positive tumor cells. The results obtained demonstrated that GE11‑EVs exhibited highly efficient targeting and drug delivery to EGFR‑positive tumor cells compared with non‑modified EVs. Furthermore, treatment with Dox‑GE11‑EVs led to a significantly inhibition of cell proliferation and increased apoptosis of EGFR‑positive tumor cells compared with Dox‑EVs and free Dox treatments. In addition, it was observed that treatment with either free Dox or Dox‑EVs exhibited a high level of cytotoxicity to normal cells, whereas treatment with Dox‑GE11‑EVs had only a limited effect on cell viability of normal cells. Taken together, the findings of the present study demonstrated that the engineered Dox‑GE11‑EVs can treat EGFR‑positive tumors more accurately and have higher safety than traditional tumor therapies.

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来源期刊
Oncology reports
Oncology reports 医学-肿瘤学
CiteScore
8.50
自引率
2.40%
发文量
187
审稿时长
3 months
期刊介绍: Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.
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