# Nano-Engineered Delivery of the Pro-Apoptotic KLA Peptide: Strategies, Synergies, and Future Directions

## TL;DR

This paper reviews how nano-engineered systems can improve the delivery and effectiveness of the KLA peptide for cancer treatment.

## Contribution

The paper provides a comprehensive overview of recent advances in nano-delivery systems for the KLA peptide to enhance its anticancer potential.

## Key findings

- Nano-engineered delivery systems improve the cellular uptake and targeting of the KLA peptide.
- Combining KLA with chemotherapeutic or immunotherapeutic agents enhances anticancer efficacy.
- Challenges remain in translating these nanotechnologies into clinical applications.

## Abstract

Antimicrobial peptides have been increasingly recognized as potential anticancer agents, with the KLA peptide (KLAKLAK2) being one of the most well-known and successful examples. The research interest in the KLA peptide is attributed to its ability to induce apoptosis in cancer cells by disrupting the mitochondrial membrane. However, the KLA peptide exhibits poor cellular uptake and it lacks targeting specificity, limiting its clinical potential in cancer therapy. In this review, recent advances in nano-engineered delivery platforms for overcoming the limitations of KLA peptides and enhancing their anticancer efficacy are discussed. Specifically, various nanocarrier systems that enable targeted delivery, controlled release and/or improved bioavailability, including pH-responsive nanosystems, photo-chemo combination liposomes, self-assembled peptide-based nanostructures, nanogel-based delivery systems, homing domain-conjugated KLA structures, inorganic-based nanoparticles, and biomimetic nanocarriers, are highlighted. Additionally, synergistic strategies for combining KLA with chemotherapeutic agents or immunotherapeutic agents to overcome resistance mechanisms in cancer cells are examined. Finally, key challenges for the clinical application of these nanotechnologies are summarized and future directions are proposed.