Open Access

An albumin‑binding domain and targeting peptide‑based recombinant protein and its enediyne‑integrated analogue exhibit directional delivery and potent inhibitory activity on pancreatic cancer with K‑ras mutation

  • Authors:
    • Weijin Sheng
    • Jing Geng
    • Liang Li
    • Yue Shang
    • Min Jiang
    • Yongsu Zhen
  • View Affiliations

  • Published online on: January 15, 2020     https://doi.org/10.3892/or.2020.7468
  • Pages: 851-863
  • Copyright: © Sheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Efficient enrichment and transmembrane transport of cytotoxic reagents are considered to be effective strategies to increase the efficiency and selectivity of antitumor drugs targeting solid tumors. In the present study, a recombinant protein ABD‑LDP‑Ec consisting of the albumin‑binding domain (ABD), the apoprotein (LDP) of lidamycin (LDM) and an EGFR‑targeting oligopeptide (Ec) was prepared by DNA recombination and bacterial fermentation, and was integrated with the enediyne chromophore (AE) of lidamycin to generate its enediyne‑integrated analogue ABD‑LDP‑Ec‑AE. ABD‑LDP‑Ec exhibited high binding capacity to both albumin and EGFR‑positive pancreatic cancer cells, and was internalized into the cytoplasm through receptor‑mediated endocytosis and albumin‑driven macropinocytosis of K‑ras mutant cells. In animal experiments, ABD‑LDP‑Ec demonstrated notable selective distribution in pancreatic carcinoma xenografts by passive targeting of albumin captured in the blood and was retained in the tumor for 48 h. ABD‑LDP‑Ec and ABD‑LDP‑Ec‑AE exhibited inhibitory activity in cell proliferation and AsPC‑1 xenograft growth, and ABD‑LDP‑Ec‑AE increased the tumor growth inhibition rate by 20% compared with natural LDM. The results indicated that the introduction of ABD‑based multi‑functional drug delivery may be an effective approach to improve the efficacy of antitumor drugs, especially for K‑ras mutant cancers.

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March 2020
Volume 43 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Sheng, W., Geng, J., Li, L., Shang, Y., Jiang, M., & Zhen, Y. (2020). An albumin‑binding domain and targeting peptide‑based recombinant protein and its enediyne‑integrated analogue exhibit directional delivery and potent inhibitory activity on pancreatic cancer with K‑ras mutation. Oncology Reports, 43, 851-863. https://doi.org/10.3892/or.2020.7468
MLA
Sheng, W., Geng, J., Li, L., Shang, Y., Jiang, M., Zhen, Y."An albumin‑binding domain and targeting peptide‑based recombinant protein and its enediyne‑integrated analogue exhibit directional delivery and potent inhibitory activity on pancreatic cancer with K‑ras mutation". Oncology Reports 43.3 (2020): 851-863.
Chicago
Sheng, W., Geng, J., Li, L., Shang, Y., Jiang, M., Zhen, Y."An albumin‑binding domain and targeting peptide‑based recombinant protein and its enediyne‑integrated analogue exhibit directional delivery and potent inhibitory activity on pancreatic cancer with K‑ras mutation". Oncology Reports 43, no. 3 (2020): 851-863. https://doi.org/10.3892/or.2020.7468