Conformation-switchable helical polypeptide eliciting selective pro-apoptotic activity for cancer therapy

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Artificial cationic helical peptides show good cell penetration.
• Current peptides exhibit nonspecific uptake due to lack of environmental responsiveness.

Purpose of the Study:

• To engineer a pH-sensitive helical polypeptide for targeted cancer therapy.
• To achieve simultaneous tumor targeting and pro-apoptotic activity.

Main Methods:

• Incorporation of pH-sensitive anion-donating groups into a helical polypeptide.
• Evaluation of pH-dependent conformational transitions and cellular uptake.
• Assessment of mitochondrial membrane disruption and apoptosis induction in cancer cells.

Main Results:

• The modified polypeptide demonstrated pH-dependent conformational changes.
• Selective targeting and uptake by cancer cells were observed.
• Disruption of mitochondrial membranes and subsequent apoptosis induction were confirmed.

Conclusions:

• The developed peptide system exhibits selective cancer cell targeting.
• pH-sensitive conformational transitions enable targeted apoptosis induction.
• This peptide therapeutic system holds promise for effective cancer therapy.