The influence of a modified p53 C-terminal peptide by using a tumor-targeting sequence on cellular apoptosis and

Xiaoye Guo1, Yiming Zhang1, Qian Li1

  • 1School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, 210009, Nanjing, P.R. China.

Insights

Restoring p53 tumor suppressor function is key. A new peptide, P462, enhances drug delivery to tumors by incorporating a tumor-targeting sequence, improving cancer treatment efficacy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • The TP53 tumor suppressor gene is frequently mutated in cancers.
  • Restoring p53 function is a promising therapeutic strategy.
  • Poor drug accumulation in tumors limits treatment effectiveness.

Purpose of the Study:

  • To enhance the anti-tumor activity of the p53 C-terminus peptide (P460).
  • To improve tumor drug delivery and accumulation.
  • To evaluate a novel peptide (P462) incorporating a tumor-targeting sequence.

Main Methods:

  • Peptide synthesis: P460 modified with Arg-Gly-Asp-Arg (RGDR) to create P462.
  • In vitro assays: Cancer cell proliferation and apoptosis.
  • In vivo studies: Tumor imaging, drug accumulation, and therapeutic efficacy.
  • Cell adhesion analysis.

Main Results:

  • P462 demonstrated enhanced inhibition of cancer cell proliferation and increased apoptosis compared to P460.
  • P462 exhibited more specific and extensive binding to tumor cells.
  • P462 showed greater tumor accumulation and improved in vivo efficacy.
  • RGDR sequence significantly enhanced cell attachment and tumor homing.

Conclusions:

  • The novel peptide P462, with its integrated RGDR tumor-targeting sequence, significantly improves anti-tumor activity.
  • P462 offers enhanced tumor homing and accumulation, addressing a key challenge in cancer therapy.
  • P462 represents a potential novel drug candidate for effective tumor treatment.

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