1-Pyrene Carboxylic Acid: An Internalization Enhancer for Short Oligoarginines.

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Delivery

Background:

• Cell membrane penetration is a significant hurdle for delivering therapeutic agents into cells.
• Cell-penetrating peptides (CPPs) offer a solution but have limitations.
• Enhancing CPP efficiency is crucial for effective intracellular drug delivery.

Purpose of the Study:

• To synthesize and evaluate novel CPPs modified with 1-pyrene carboxylic acid (PCA) for enhanced cellular internalization.
• To investigate the impact of PCA placement (N-terminus vs. side chain) on oligoarginine CPP activity.
• To explore the internalization mechanisms of PCA-modified CPPs in tumor cell lines.

Main Methods:

• Synthesis of oligoarginine peptides with 1-pyrene carboxylic acid (PCA) modifications at various positions.
• Assessment of peptide internalization efficiency in different tumor cell lines.
• Analysis of the endocytic pathways involved in peptide uptake.

Main Results:

• Novel PCA-modified oligoarginines demonstrated significant internalization into tumor cells.
• The position of PCA influenced the internalization efficiency of the peptide derivatives.
• Multiple endocytic pathways were identified as contributing to the uptake mechanism.
• Short PCA-modified oligoarginines exhibited internalization comparable to well-established CPPs like octaarginine.

Conclusions:

• 1-Pyrene carboxylic acid (PCA) modification is an effective strategy to enhance the internalization of oligoarginines.
• PCA-modified short oligoarginines show potential as efficient CPPs for therapeutic delivery.
• These findings offer opportunities for designing improved CPPs for targeted drug delivery applications.