Albumin-Mediated Delivery of Bioactive Peptides for Pancreatic Cancer Therapy
Albumin-Mediated Delivery of Bioactive Peptides for Pancreatic Cancer Therapy
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白蛋白介导的生物活性肽递送用于胰腺癌治疗
DOI：
10.1002/adtp.202000003
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发表时间：
2020-04-29
影响因子：
4.6
通讯作者：
Xu, Jian
中科院分区：
文献类型：
--
作者：
Du, Yue;Shang, Boyang;Xu, Jian
生物活性肽是有前途的药物治疗应用;然而，它们的小尺寸导致稳定性差，生物利用度低，肾清除快，因此广泛使用受到限制。为了解决这些问题，需要将肽融合或缀合到合适的分子支架上。在此，人血清白蛋白（HSA）用作人β-防御素-2肽（HBD 2）的递送载体，用于生产HSA递送的防御素复合物（ADDC），以促进其细胞摄取和转运至细胞内靶标。融合或偶联可以提高HBD 2的稳定性，延长其循环时间，促进其在肿瘤中的蓄积，从而提高治疗效果。在本文中，ADDC作为一种保护性结构来对抗恶劣的外部环境，并作为一种被动的肿瘤靶向剂。数据显示，ADDC与临床相关药物如多柔比星、吉西他滨、顺铂和西妥昔单抗的组合显著增加ADDC对人胰腺癌细胞的细胞毒性。生物信息学分析还表明，ADDC可能影响胰腺癌细胞的代谢过程、基因转录和细胞凋亡。总的来说，ADDC在胰腺癌小鼠模型中表现出肿瘤特异性靶向能力、低全身毒性和增强的抗肿瘤功效。
Bioactive peptides are promising agents for therapeutic applications; however, their small size leads to poor stability, low bioavailability, and rapid renal clearance, so the widespread use is limited. To address these issues, fusing or conjugating peptides to suitable molecular scaffolds is required. Here, human serum albumin (HSA) is used as a delivery carrier for human β‐defensin‐2 peptide (HBD2) in production of HSA‐delivered defensin complex (ADDC) to facilitate its cellular uptake and transport to intracellular targets. Fusion or conjugation can improve the stability of HBD2, as well as extend its circulation time and promote its accumulation in tumors, thereby enhancing the therapeutic efficacy. Herein, ADDC functions as a protective structure against the harsh external environment and serves as a passive tumor‐targeting agent. The data show that the combination of ADDC with clinically relevant drugs, such as Doxorubicin, Gemcitabine, Cisplatin, and Cetuximab, significantly increases the cytotoxicity of ADDC toward human pancreatic cancer cells. Bioinformatics analysis also reveals that ADDC may affect the metabolic processes, gene transcription, and apoptosis of pancreatic cancer cells. Collectively, ADDC exhibits tumor‐specific targeting capability, low systemic toxicity, and enhanced antitumor efficacy in a mouse model of pancreatic cancer.