Shallot Leaf Extract-Loaded Nanostructured Lipid Carrier as a Preliminary Platform for STMN1-Targeted Screening and Macrophage Phagocytic Activity Enhancement
DOI:
https://doi.org/10.23917/pharmacon.v23i1.16383Keywords:
Lipid carriers, Macrophage phagocytosis, Molecular docking, Nanostructured, Shallot leaf extract, STMN1Abstract
Cancer metastasis remains a major therapeutic challenge involving molecular dysregulation and tumor–microenvironment interactions. Stathmin 1 (STMN1), a microtubule-destabilizing regulator related to cell motility and tumor aggressiveness, is relevant for preliminary anti-metastasis-oriented screening. Nanostructured lipid carriers (NLC) may improve the dispersion and delivery performance of natural-product extracts. This study formulated shallot leaf (Allium cepa L.) extract into an NLC dispersion using emulsification–ultrasonication under homogenized and non-homogenized conditions, followed by PSA/DLS and SEM characterization. Phytochemical candidates curated from databases and literature were docked to STMN1 to identify ligands with favorable predicted binding profiles. Macrophage phagocytic function was evaluated using a latex-bead assay at 0, 5, and 10 µL. PSA/DLS and SEM indicated particulate structures, but particle-size variation and aggregation suggested the need for further formulation optimization and stability evaluation. Docking ranked sinapic acid (−7.5 kcal/mol) and ferulic acid (−7.4 kcal/mol) as the best phenolic candidates among the tested ligands, although the GDP control showed stronger predicted affinity. Phagocytic capacity increased from 33.5% (0 µL) to 37% (5 µL) and 91% (10 µL), while the phagocytic index increased from 0.63 to 0.77 and 4.50, respectively. The 10 µL dose was the most responsive condition for enhancing macrophage phagocytic activity. These findings should be interpreted as preliminary evidence of STMN1-oriented in silico prioritization and macrophage functional enhancement, not direct proof of anti-metastatic activity or M2 macrophage inhibition.
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Agu, P. C., Afiukwa, C. A., Orji, O. U., Ezeh, E. M., Ofoke, I. H., Ogbu, C. O., Ugwuja, E. I., & Aja, P. M. (2023). Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Sci. Rep., 13(1), 13398.
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 3(74). https://doi.org/10.3322/caac.21834
Bresch, H., Hodoroaba, V.-D., Schmidt Alexandra and Rasmussen, K., & Rauscher, H. (2022). Counting small particles in electron microscopy images-proposal for rules and their application in practice. Nanomaterials (Basel), 12(13), 2238.
Calderon-Jacinto, R., Matricardi, P., Gueguen, V., Pavon-Djavid, G., Pauthe, E., & Rodriguez-Ruiz, V. (2022). Dual Nanostructured Lipid Carriers/Hydrogel System for Delivery of Curcumin for Topical Skin Applications. Biomolecules, 12(6).
Chauhan, I., Yasir, M., Verma, M., & Singh, A. P. (2020). Nanostructured lipid carriers: A groundbreaking approach for transdermal drug delivery. Adv. Pharm. Bull., 10(2), 150–165.
De Jesus, A., Pusec, C. M., Nguyen, T., Keyhani-Nejad, F., Gao, P., Weinberg, S. E., & Ardehali, H. (2022). Optimized protocol to isolate primary mouse peritoneal macrophage metabolites. STAR Protoc., 3(4), 101668.
Duke, J. A. (2016). Dr. Duke’s phytochemical and ethnobotanical databases. Ag Data Commons.
Elkhateeb, O., Badawy, M. E. I., Tohamy, H. G., Abou-Ahmed, H., El-Kammar, M., & Elkhenany, H. (2023). Curcumin-infused nanostructured lipid carriers: a promising strategy for enhancing skin regeneration and combating microbial infection. BMC Vet. Res., 19(1), 206.
Fakoya, A. O., Naeem, A., & Pierre, L. (2025). Histology, alveolar macrophages. In StatPearls. StatPearls Publishing.
Friedman-DeLuca, M., Karagiannis, G. S., Condeelis, J. S., Oktay, M. H., & Entenberg, D. (2024). Macrophages in tumor cell migration and metastasis. Frontiers in Immunology, Volume 15-2024. https://doi.org/10.3389/fimmu.2024.1494462
Green, M. R., & Sambrook, J. (2019). Estimation of cell number by hemocytometry counting. Cold Spring Harb. Protoc., 2019(11), db.prot097980.
Hackley, V., & Clogston, J. (2020). NIST - NCL Joint Assay Protocol, PCC-1. NCIP Hub.
Imran, M., Iqubal, M. K., Imtiyaz Khalid and Saleem, S., Mittal, S., Rizvi M Moshahid A and Ali, J., & Baboota, S. (2020). Topical nanostructured lipid carrier gel of quercetin and resveratrol: Formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer. Int. J. Pharm., 587(119705), 119705.
Iwar, K., Ochar, K., Seo, Y. A., Ha, B.-K., & Kim, S.-H. (2024). Alliums as potential antioxidants and anticancer agents. Int. J. Mol. Sci., 25(15), 8079.
Jeitler, R., Glader, C., König, G., Kaplan, J., Tetyczka, C., Remmelgas, J., Mußbacher, M., Fröhlich, E., & Roblegg, E. (2024). On the Structure, Stability, and Cell Uptake of Nanostructured Lipid Carriers for Drug Delivery. Molecular Pharmaceutics, 21(7), 3674–3683.
https://doi.org/10.1021/acs.molpharmaceut.4c00392
Khatua, S., Simal-Gandara, J., & Acharya, K. (2022). Understanding immune-modulatory efficacy in vitro. Chem. Biol. Interact., 352(109776), 109776.
Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky Leonid and Zhang, J., & Bolton, E. E. (2023). PubChem 2023 update. Nucleic Acids Res., 51(D1), D1373–D1380.
Krakowska-Sieprawska, A., Kiełbasa, A., Rafińska, K., Ligor, M., & Buszewski, B. (2022). Modern methods of pre-treatment of plant material for the extraction of bioactive compounds. Molecules, 27(3), 730.
Kumari, M., Gohil, D., & Sadhu, P. (2026). Nanostructured lipid carriers for topical drug delivery: A comprehensive review of design, mechanisms, and therapeutic advances. Next Nanotechnology, 9, 100367. https://doi.org/10.1016/j.nxnano.2026.100367
Lim, S. H., Wong, T. W., & Tay, W. X. (2024). Overcoming colloidal nanoparticle aggregation in biological milieu for cancer therapeutic delivery: Perspectives of materials and particle design. Advances in Colloid and Interface Science, 325, 103094. https://doi.org/https://doi.org/10.1016/j.cis.2024.103094
Liu, R., Liang, X., Guo, H., Li, S., Yao, W., Dong, C., Wu, J., Lu, Y., Tang, J., & Zhang, H. (2023). STNM1 in human cancers: role, function and potential therapy sensitizer. Cellular Signalling, 109, 110775. https://doi.org/https://doi.org/10.1016/j.cellsig.2023.110775
Papagiouvannis, G., Theodosis-Nobelos, P., & Rekka, E. A. (2024). Trolox, Ferulic, Sinapic, and Cinnamic Acid Derivatives of Proline and GABA with Antioxidant and/or Anti-Inflammatory Properties. Molecules, 29(16). https://doi.org/10.3390/molecules29163763
Pavlova, E., Shaposhnikova, D., Petrichuk, S., Radygina, T., & Erokhina, M. (2023). Quantitative analysis of latex beads phagocytosis by human macrophages using imaging flow cytometry with extended depth of field (EDF). Methods Mol. Biol., 2635, 203–215.
Riezk, A., O’Keeffe, A., Van Bocxlaer, K., Yardley, V., & Croft, S. L. (2025). Comparative assessment of macrophage responses and antileishmanial efficacy in dynamic vs. Static culture systems utilizing chitosan-based formulations. PLOS ONE, 20(3), e0319610-. https://doi.org/10.1371/journal.pone.0319610
Theodosis-Nobelos, P., Papagiouvannis, G., & Rekka, E. A. (2023). Ferulic, Sinapic, 3,4-Dimethoxycinnamic Acid and Indomethacin Derivatives with Antioxidant, Anti-Inflammatory and Hypolipidemic Functionality. Antioxidants, 12(7). https://doi.org/10.3390/antiox12071436
Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 31(2), 455–461.
Ueno, T., Yamamoto, Y., & Kawasaki, K. (2021). Phagocytosis of microparticles increases responsiveness of macrophage-like cell lines U937 and THP-1 to bacterial lipopolysaccharide and lipopeptide. Scientific Reports, 11(1), 6782. https://doi.org/10.1038/s41598-021-86202-5
Varadi, M., Anyango, S., Deshpande, M., Nair, S., Natassia, C., Yordanova, G., Yuan, D., Stroe, O., Wood, G., Laydon, A., Žídek, A., Green, T., Tunyasuvunakool, K., Petersen, S., Jumper, J., Clancy, E., Green, R.,
Vora, A., Lutfi, M., … Velankar, S. (2022). AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Research, 50(D1), D439–D444. https://doi.org/10.1093/nar/gkab1061
Velez-Hoyos, A., & Jimenez-tobon, G. A. (2022). Highlights of infectious agents in tissue. Pathology, 54(2), 217–224. https://doi.org/https://doi.org/10.1016/j.pathol.2021.10.004
Zeng, L., Lyu, X., Yuan, J., Chen, Y., Wen, H., Zhang, L., Shi, J., Liu, B., Li, W., & Yang, S. (2024). STMN1 promotes tumor metastasis in non-small cell lung cancer through microtubule-dependent and nonmicrotubule-dependent pathways. Int. J. Biol. Sci., 20(4), 1509–1527.
