# Doxorubicin delivery by pYEEIE peptide-functionalized rhodiola rosea-derived exosome-like nanovesicles for targeted melanoma therapy

## TL;DR

A new drug delivery system using plant-derived nanovesicles loaded with doxorubicin shows effective and safe treatment for melanoma in mice.

## Contribution

A novel targeted delivery system using pYEEIE peptide-functionalized Rhodiola rosea-derived nanovesicles loaded with doxorubicin is introduced for melanoma therapy.

## Key findings

- pYEEIE-RELNs-DOX showed superior tumor targeting and inhibited melanoma growth more effectively than free DOX.
- The system caused no toxicity to major organs, unlike free DOX which induced cardiac damage.
- Normal serum ALT and AST levels indicated no liver cell damage with pYEEIE-RELNs-DOX.

## Abstract

Melanoma is the most common cause of skin cancer-related deaths due to its aggressive nature. Plant-derived exosome-like nanovesicles (PELNs) are promising natural nanoparticles for therapeutic applications owing to their biocompatibility and diverse bioactive components. However, research on Rhodiola rosea-derived exosome-like nanovesicles (RELNs) remains limited.

This study evaluated the therapeutic efficacy and safety of a novel targeted drug delivery system, pYEEIE peptide-functionalized RELNs loaded with doxorubicin (DOX) (pYEEIE-RELNs-DOX), in melanoma-bearing mice.

Fluorescence imaging and histopathological assessments demonstrated that pYEEIE-RELNs-DOX exhibited superior tumor-targeting ability and significantly inhibited melanoma growth compared to free DOX and non-targeted RELNs-DOX. Importantly, pYEEIE-RELNs-DOX showed no toxicity to major organs (heart, liver, spleen, lungs, and kidneys), whereas free DOX induced cardiac tissue damage. Meanwhile, the serum ALT and AST levels remained normal, indicating no liver cell damage.

These findings highlight the potential of pYEEIE-RELNs-DOX as a low-toxicity, high-efficacy targeted delivery system for melanoma therapy, providing a foundation for clinical translation.