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Enhanced Tumor-Targeted Delivery of Arginine-Rich Peptides via a Positive Feedback Loop Orchestrated by

Minghai Ma1, Xing Li2, Minxuan Jing1

  • 1Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 11, 2024
PubMed

Insights

Hendeca-arginine peptides (R11) target bladder cancer by engaging the Piezo1/integrin β1 axis. This interaction enhances cellular uptake and prevents lysosomal degradation, improving peptide drug delivery for cancer therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Peptide-based drugs offer promise for cancer treatment but their precise targeting mechanisms remain unclear.
  • Lysosomal entrapment can limit the efficacy of peptide therapeutics.
  • Understanding these mechanisms is crucial for designing effective peptide-drug conjugates.

Purpose of the Study:

  • To synthesize hendeca-arginine peptides (R11) for targeted delivery in bladder carcinoma (BC).
  • To investigate the targeting efficiency and elucidate the mechanism of R11 peptide delivery.
  • To refine the design and efficacy of peptide-based therapeutics.

Main Methods:

  • Synthesis of hendeca-arginine peptides (R11).
  • Investigation of R11 peptide targeting in bladder carcinoma models.
  • Elucidation of the Piezo1/integrin β1 signaling pathway's role in R11 uptake.
  • Analysis of R11 peptide interactions with integrin β1 and lysosomal pathways.

Main Results:

  • The Piezo1/integrin β1 signaling axis significantly facilitates R11 peptide tumor targeting via macropinocytosis.
  • R11 peptides form hydrogen bonds with integrin β1, enhancing tumor cell targeting and penetration.
  • R11 peptides protect integrin β1 from lysosomal degradation, promoting its recycling.
  • A positive feedback loop involving R11, Piezo1, and integrin β1 enhances cellular uptake and transport.

Conclusions:

  • The Piezo1/integrin β1 axis is a key mediator of R11 peptide tumor-targeted delivery.
  • R11 peptides promote their own uptake and transport through a positive feedback mechanism.
  • These findings offer new strategies for modifying peptide drugs to enhance cancer therapy efficacy.
Keywords:
arginine‐rich peptidesintegrin β1piezo1positive feedback looptumor‐targeted delivery

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