ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1619998
Doxorubicin Delivery by pYEEIE Peptide-Functionalized Rhodiola rosea-Derived Exosome-Like Nanovesicles for Targeted Melanoma Therapy
Provisionally accepted
Chen Wang1*
Duan Meitao1
Binbin Chen2Xue Yi1
Ahmed Mahal3Linwei Song1Moxun Xu1
Ahmad J Obaidullah4Shuwei Yu1- 1Xiamen Medical College, Xiamen, China
- 2Xiamen Xianyue Hospital, Xiamen, China
- 3Cihan University-Erbil, Erbil, Iraq
- 4King Saud University, Riyadh, Saudi Arabia
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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.
Keywords: Rhodiola rosea, Rhodiola-derived exosome-like nanovesicles, Doxorubicin, pYEEIE peptide, drug delivery system, Melanoma
Received: 29 Apr 2025; Accepted: 04 Jul 2025.
Copyright: © 2025 Wang, Meitao, Chen, Yi, Mahal, Song, Xu, Obaidullah and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chen Wang, Xiamen Medical College, Xiamen, China
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