The Potential of Nano-Formulated Natural Drugs in Melanoma Treatment: A Review of Pharmacological Efficacy and Mechanistic Insights

Melanoma is a very aggressive skin cancer; its treatment bears great challenges, hence the interest in new therapeutic approaches is growing. In this review, potential nano-formulated natural drugs from plants such as Ginseng, Pistacia lentiscus, Amaranthus hypochondriacus, and Cannabis sativa in the treatment of melanoma are discussed. Various characteristics of nanoformulations, including liposomes and nanoemulsions, are discussed with respect to their ability in enhancing drug delivery and bioavailability. Key mechanisms of action including reactive oxygen species modulation, apoptotic signaling induction, immune modulation through TLR4/MyD88, and inhibition of angiogenesis by VEGF pathways are discussed. Although these natural nanoformulations show promise in improving therapeutic outcomes, challenges related to their clinical application and safety persist. 

The application of natural-based compounds, coupled with nanotechnological tools, offers a promising approach for advancing melanoma management. By utilizing nano-formulated natural compounds, these therapies can overcome the limitations of conventional treatments, including low bioavailability, high toxicity, and poor targeting. The integration of nanocarriers enables enhanced targeting, sustained release, and immune modulation, all of which are crucial for effectively addressing the complexities of melanoma. While challenges such as large-scale production and clinical validation persist, ongoing advancements in both natural compounds and nanotechnologies hold the potential to revolutionize melanoma treatment, providing safer, more effective, and highly targeted therapeutic options.

Liposomes. nanofibers, nanoemulsions, nanoparticles, self-assembling and biomimetic carriers are discussed without mentioning cyclodextrin-based nanoformulations. A quick search in the Scopus database (scopus.com) gave the 316 hits for keywords: cyclodextrin +melanoma, but most of these papers deal with cholesterol modifying effect of CDs and not on their delivery applications for plant-derived medicines. Some examples:

• Triterpenoid saponin-based supramolecular host-guest injectable hydrogels [2]
• Phyllacanthone/SBECD conplex [3]
• Microneedle patch for curcumin transdermal delivery [4]

[1] Wang B, Wang Y. The Potential of Nano-Formulated Natural Drugs in Melanoma Treatment: A Review of Pharmacological Efficacy and Mechanistic Insights. Int J Nanomedicine. 2025;20:3527-3539
https://doi.org/10.2147/IJN.S505394

[2] Ramya Mathiyalagan, Mohanapriya Murugesan, Zelika Mega Ramadhania, et al. (2024) Triterpenoid saponin-based supramolecular host-guest injectable hydrogels inhibit the growth of melanoma via ROS-mediated apoptosis. Materials Science and Engineering: R: Reports 160, 100824.
https://doi.org/10.1016/j.mser.2024.100824

[3] https://cyclodextrinnews.com/2023/11/23/anti-melanoma-potential-of-inclusion-complexes-containing-phyllacanthone-in-%ce%b2-cyclodextrin-and-sulfobutyl-ether-%ce%b2-cyclodextrin/

[4] https://cyclodextrinnews.com/2020/08/17/biodegradable-β-‐cyclodextrin-conjugated-gelatin-methacryloyl-microneedle-for-delivery-of-water‐insoluble-drug/

Featured image: wikipedia