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Peptide-derived Method to Transport Genes and Proteins Across Cellular and Organellar Barriers in Plants
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Improved Protein Toxin Delivery Based on ATTEMPTS Systems.

Yingzhi Chen1, Meng Zhang1, Kyoung Ah Min2

  • 1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Current Drug Targets
|March 7, 2017
PubMed
Summary

Novel cell-penetrating peptide (CPP)-modified systems enhance protein toxin delivery for cancer therapy. These systems improve tumor targeting and reduce toxicity, showing promise for clinical translation in anticancer treatment.

Keywords:
Protein toxincell-penetrating peptide (CPP)geloninimmunotoxinribosome-inactivating proteintumortargeting delivery.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Ribosome-inactivating proteins (RIPs) are potent toxins that inhibit protein synthesis and induce cell death.
  • RIPs show promise for anti-tumor therapy but face limitations like poor cell permeability, non-specific targeting, and immunogenicity.
  • Current immunotoxins, while improving targeting, still struggle with immunogenicity and deep tumor penetration.

Purpose of the Study:

  • To develop novel cell-penetrating peptide (CPP)-modified ATTEMPTS systems for improved protein toxin delivery.
  • To combine CPP-mediated penetration with antibody-mediated tumor targeting and triggerable drug release for effective and safe delivery.
  • To overcome the limitations of existing immunotoxins in cancer treatment.

Main Methods:

  • Development of CPP-modified ATTEMPTS systems integrating CPPs, antibodies, and triggerable release mechanisms.
  • Evaluation of protamine-triggered CPP-toxin release and CPP-mediated cellular uptake and cytotoxicity.
  • Assessment of antibody-mediated in vivo tumor targeting and tumor growth suppression.

Main Results:

  • The CPP-modified ATTEMPTS systems demonstrated effective protamine-triggered CPP-toxin release.
  • Enhanced CPP-mediated cellular uptake and cytotoxicity were observed.
  • Significant in vivo tumor growth suppression with limited systemic toxicity was achieved through antibody-mediated targeting.

Conclusions:

  • CPP-modified ATTEMPTS systems represent a proof-of-concept for CPP-based protein toxin delivery with triggerable antibody targeting.
  • These systems improve the druggability of protein toxin drugs for anticancer treatment.
  • The developed systems show potential for clinical translation in anticancer therapy.