Scholarlink

Objective <p>Bioactive peptides derived from natural or synthetic sources have shown significant potential for cancer therapy; however, their clinical application is often limited by poor tumor selectivity and systemic toxicity. In this work, we aim to develop a multifunctional antitumor peptide with enhanced tumor- targeting capability and therapeutic efficacy.</p> Methods <p>A cationic antimicrobial peptide (AMP, (KKWW)<sub>2</sub>&#xa0;K-NH<sub>2</sub>) was chemically modified via cysteine-mediated conjugation with 4-vinylphenylboronic acid, yielding the phenylboronic acid-conjugated AMP (PBA-AMP). Molecular dynamics (MD) simulations were performed to evaluate peptide-membrane interactions. Cellular uptake, cytotoxicity, and <i>in vivo</i> tumor-targeting and antitumor efficacy were assessed using MCF-7 cells and 4T1 tumor-bearing mice.</p> Results <p>MD simulations demonstrated that PBA-AMP exhibited rapid and stable binding to tumor cell membranes, maintaining consistent membrane interactions over a 50&#xa0;ns simulation. Cellular studies revealed enhanced cellular uptake and increased cytotoxicity of PBA-AMP against MCF-7 breast cancer cell line (IC<sub>50</sub> = 38.46&#xa0;μM) compared to naive AMP (IC<sub>50</sub> = 110&#xa0;μM). <i>In vivo</i> imaging confirmed selective and prolonged tumor accumulation of PBA-AMP. Treatment with PBA-AMP significantly suppressed tumor growth in 4T1 tumor-bearing mice without observable systemic toxicity.</p> Conclusions <p>This study presents a rational design strategy for engineering tumor-selective, microenvironment-responsive therapeutic peptides. PBA-AMP represents a promising candidate for targeted cancer therapy, offering improved efficacy and reduced off-target effects.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Rational Design of a Bioconjugated Antitumor Peptide with Tumor-Selective Targeting and Microenvironment-Responsive Activation

  • 期刊论文

  • 发表日期：

    2025年12月10日

查看全文
  • Chunlai Feng,
  • Wen Deng,
  • Min Cai,
  • Yujiao Hu,
  • Wenyan Liang,
  • Hangyu Dong,
  • Mengjie Rui

摘要

Objective

Bioactive peptides derived from natural or synthetic sources have shown significant potential for cancer therapy; however, their clinical application is often limited by poor tumor selectivity and systemic toxicity. In this work, we aim to develop a multifunctional antitumor peptide with enhanced tumor- targeting capability and therapeutic efficacy.

Methods

A cationic antimicrobial peptide (AMP, (KKWW)2 K-NH2) was chemically modified via cysteine-mediated conjugation with 4-vinylphenylboronic acid, yielding the phenylboronic acid-conjugated AMP (PBA-AMP). Molecular dynamics (MD) simulations were performed to evaluate peptide-membrane interactions. Cellular uptake, cytotoxicity, and in vivo tumor-targeting and antitumor efficacy were assessed using MCF-7 cells and 4T1 tumor-bearing mice.

Results

MD simulations demonstrated that PBA-AMP exhibited rapid and stable binding to tumor cell membranes, maintaining consistent membrane interactions over a 50 ns simulation. Cellular studies revealed enhanced cellular uptake and increased cytotoxicity of PBA-AMP against MCF-7 breast cancer cell line (IC50 = 38.46 μM) compared to naive AMP (IC50 = 110 μM). In vivo imaging confirmed selective and prolonged tumor accumulation of PBA-AMP. Treatment with PBA-AMP significantly suppressed tumor growth in 4T1 tumor-bearing mice without observable systemic toxicity.

Conclusions

This study presents a rational design strategy for engineering tumor-selective, microenvironment-responsive therapeutic peptides. PBA-AMP represents a promising candidate for targeted cancer therapy, offering improved efficacy and reduced off-target effects.