Applied Chemical Engineering

Development of bioactive CS-g-P(AA-DEABA)/EEP nanocomposites with selective anticancer activity against colon cancer cells and enhanced wound healing properties

Zahraa Khairi Shamran

Department of Chemistry, College of Science, University of Al-Qadisiyah, Diwaniya, 58002, Iraq

Muqdad Irhaeem Kadhim

Department of Chemistry, College of Science, University of Al-Qadisiyah, Diwaniya, 58002, Iraq

DOI: https://doi.org/10.59429/ace.v8i4.5765

Keywords: Chitosan hydrogel nanocomposite; Propolis extract; DEABA Schiff base; Selective cytotoxicity; Colon cancer therapy, Wound healing acceleration

---

Abstract

Background: Cancer treatment often faces limitations due to lack of selectivity and toxicity toward normal cells. The combination of natural and synthetic bioactive agents offers a promising route to overcome these drawbacks. Aim: To synthesize and evaluate a novel chitosan-based nanocomposite integrating a thiazole-derived Schiff base (DEABA) and ethanolic propolis extract (EEP) for selective anticancer activity and wound healing. Methods: The DEABA compound was synthesized via two-step condensation and confirmed by NMR and FTIR analyses. The CS-g-P(AA-DEABA)/EEP nanocomposite was prepared through free radical polymerization and characterized by XRD, SEM, AFM, and TGA. Cytotoxicity was tested on LS147T colon cancer and WRL-68 normal cells, and wound-healing efficiency was assessed in a mouse model. Results: The nanocomposite exhibited a crystalline–amorphous hybrid structure with enhanced surface roughness and stability up to 200 °C. It showed selective cytotoxicity toward LS147T cells (IC₅₀ = 100–120 µg/mL) and promoted wound closure by 89.7% ± 3.8% on day 5 with minimal inflammation. Conclusion: The novel CS-g-P(AA-DEABA)/EEP nanocomposite demonstrates dual bioactivity for colon cancer inhibition and tissue regeneration, confirming its potential for biomedical and nanotherapeutic applications.

---

References

[1]. Sung, H., et al. (2021). Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209-249.

[2]. Mitchell, M.J., et al. (2021). Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery, 20(2), 101-124.

[3]. Senapati, S., et al. (2018). Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduction and Targeted Therapy, 3, 7.

[4]. Li, J., & Mooney, D.J. (2016). Designing hydrogels for controlled drug delivery. Nature Reviews Materials, 1(12), 16071.

[5]. Zhao, X., et al. (2020). Injectable stem cell-laden photocrosslinkable microspheres fabricated using microfluidics for rapid generation of osteogenic tissue constructs. Advanced Functional Materials, 30(6), 1909267.

[6]. Ayati, A., et al. (2015). Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery. European Journal of Medicinal Chemistry, 97, 699-718.

[7]. Boulechfar, C., et al. (2023). Schiff bases and their metal complexes: a review on the history, synthesis, and applications. Inorganic Chemistry Communications, 150, 110451.

[8]. Bankova, V., et al. (2014). Propolis: Recent advances in chemistry and plant origin. Apidologie, 45(6), 696-710.

[9]. Zaccara, S., et al. (2016). Caffeic acid phenethyl ester: A natural antioxidant and anti-inflammatory compound with potential therapeutic applications. Current Topics in Medicinal Chemistry, 16(10), 1097-1109.

[10]. Krizkova, J., et al. (2019). Biological effects of propolis on human health. Biomedicine & Pharmacotherapy, 117, 109081.

[11]. Fan, Y., et al. (2020). Biomaterial-based strategies for cancer immunotherapy. Advanced Materials, 32(45), 2002440.

[12]. Aranaz, I., et al. (2021). Chitosan: An overview of its properties and applications. Polymers, 13(19), 3256.

[13]. Bashir, S., et al. (2020). Fundamental concepts of hydrogels: Synthesis, properties, and their applications. Polymers, 12(11), 2702.

[14]. Chen, G., et al. (2018). Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy. Chemical Reviews, 116(5), 2826-2885.

[15]. Shi, J., et al. (2017). Cancer nanomedicine: Progress, challenges and opportunities. Nature Reviews Cancer, 17(1), 20-37.

[16]. Manzano, M., & Vallet-Regí, M. (2020). Mesoporous silica nanoparticles for drug delivery. Advanced Functional Materials, 30(2), 1902634.

[17]. Mahdi, M.A., et al. (2023). Synthesis, characterization and study the biological activity for new Schiff base compound. Journal of Nanostructures, 13(2), 245-256.

[18]. Shameem, R., et al. (2017). Phytochemical screening by FTIR spectroscopic analysis of methanol leaf extract. Journal of Ayurvedic and Herbal Medicine, 3(1), 22-28.

[19]. Tsou, C.H., et al. (2022). Highly resilient antibacterial composite polyvinyl alcohol hydrogels reinforced with CNT-NZnO. Journal of Polymer Research, 29(10), 412.

[20]. Hanna, D.H., & Saad, G.R. (2019). Encapsulation of ciprofloxacin within modified xanthan gum-chitosan based hydrogel for drug delivery. Bioorganic Chemistry, 84, 115-124.

[21]. Sumrra, S. H., et al. (2020). Efficient synthesis, characterization, and in vitro bactericidal studies of unsymmetrically substituted triazole-derived Schiff base ligand. Monatshefte für Chemie, 151, 549-557.

[22]. Bal, M., & Köse, A. (2024). Schiff bases containing 1,2,3-triazole group and phenanthroline: Synthesis, characterization, and investigation of DNA binding properties. Journal of Photochemistry and Photobiology A: Chemistry, 448, 115320.

[23]. Nimal, R., et al. (2020). Thermodynamic characterisation of triazolylimino-DNA interaction by UV–Vis spectroscopy. Journal of Photochemistry and Photobiology, 2, 100006.

[24]. Joshi, R., et al. (2024). Combined experimental and theoretical studies of diorganotin(IV) complexes of 1,2,4-triazole based Schiff base. Journal of Molecular Structure, 1296, 136824.

[25]. Sancak, K., et al. (2007). Cu(II), Ni(II) and Fe(II) complexes with a new substituted [1,2,4] triazole Schiff base. Transition Metal Chemistry, 32, 16-22.

[26]. Issa, Y. M., et al. (2009). ¹H NMR, ¹³C NMR and mass spectral studies of some Schiff bases derived from 3-amino-1,2,4-triazole. Spectrochimica Acta Part A, 74(4), 902-910.

[27]. Kanagavalli, A., et al. (2023). Synthesis, electronic structure, UV–vis, wave function, and molecular docking studies of Schiff base. Polycyclic Aromatic Compounds, 43(10), 8710-8728.

[28]. Nagesh, G. Y., et al. (2015). Synthesis, characterization, thermal study and biological evaluation of Cu(II), Co(II), Ni(II) and Zn(II) complexes. Journal of Molecular Structure, 1079, 423-432.

[29]. Ravindra Reddy, T., et al. (2017). Spectroscopic characterization of bentonite. Journal of Lasers, Optics & Photonics, 4(3), 1-7.

[30]. Sharma, P., et al. (2023). Non-toxic and biodegradable κ-carrageenan/ZnO hydrogel for adsorptive removal of norfloxacin. International Journal of Biological Macromolecules, 238, 124145.

[31]. Dehli, F., et al. (2021). Gelatin-based foamed and non-foamed hydrogels for sorption and controlled release of metoprolol. ACS Applied Polymer Materials, 3(11), 5674-5682.

[32]. Hu, X., et al. (2015). Preparation and characterization of a novel pH-sensitive Salecan-g-poly(acrylic acid) hydrogel. Journal of Materials Chemistry B, 3(13), 2685-2697.

[33]. Tyliszczak, B., et al. (2019). Novel hydrogels modified with xanthan gum–synthesis and characterization. Technical Transactions, 116(1), 79-91.

[34]. Salehi, M. M., et al. (2024). Performance of magnetic nanocomposite based on Xanthan gum-grafted-poly(acrylamide). Chemosphere, 142548.

[35]. Jadav, M., et al. (2023). Advances in xanthan gum-based systems for delivery of therapeutic agents. Pharmaceutics, 15(2), 402.

[36]. Dadou, S. M., et al. (2019). Elucidation of controlled-release behavior of metoprolol succinate from xanthan gum/chitosan polymers. ACS Biomaterials Science & Engineering, 6(1), 21-37.

[37]. Yang, Q., & Zhao, L. R. (2008). Characterization of nano-layered multilayer coatings using modified Bragg law. Materials Characterization, 59(9), 1285-1291.

[38]. Cuevas, J., et al. (2022). Bentonite powder XRD quantitative analysis using Rietveld refinement. Minerals, 12(6), 772.

[39]. Zhang, B., et al. (2022). Preparation and swelling inhibition of mixed metal hydroxide to bentonite clay. Minerals, 12(4), 459.

[40]. Hebbar, R. S., et al. (2018). Removal of metal ions and humic acids through polyetherimide membrane with grafted bentonite clay. Scientific Reports, 8(1), 4665.

[41]. Thakur, S., & Arotiba, O. (2018). Synthesis, characterization and adsorption studies of an acrylic acid-grafted sodium alginate-based TiO₂ hydrogel. Adsorption Science & Technology, 36(1-2), 458-477.

[42]. Kadhim, M. I., & Jabbar, A. H. (2020). Synthesis of nucleotide - Amino acids via new branched chain sugar. Systematic Reviews in Pharmacy, 11(6), 404-408.

[43]. Dur, S., Husein, I., Kadhim, M. I., Mohammed, H. S., Elveny, M., Syah, R., et al. (2020). An optimally solving dentistry internal purity in heat polymerized acrylic resin with different polymerization methods. Systematic Reviews in Pharmacy, 11(3), 974-980.

[44]. Anjum, S. I., et al. (2019). Composition and functional properties of propolis (bee glue): A review. Saudi Journal of Biological Sciences, 26(7), 1695-1703.

[45]. Khakpour, R., & Tahermansouri, H. (2018). Synthesis, characterization and study of sorption parameters of multi-walled carbon nanotubes/chitosan nanocomposite. International Journal of Biological Macromolecules, 109, 598-610.

[46]. Hameed, K. A. A., & Radia, N. D. (2022). The synthesis of graphene oxide/hydrogel composites and kinetic study adsorb Eosin B efficiently. NeuroQuantology, 20(3), 32.

[47]. Yasir, A. F., & Jamel, H. O. (2023). Synthesis of a new DPTYEAP ligand and its complexes with assessments on physical properties. Indonesian Journal of Chemistry.

[48]. Salman, S. R., & Jamel, H. O. (2020). Preparation, characterization and evaluation of biological activity of new ligand derived from 2-mercaptobenzimidazole. Solid State Technology, 63(1), 1612-1626.

[49]. Dawood, M. N., & Jamel, H. O. (2022). Synthesis, characterization and evaluation of biological activity of new ligand derived from 4-aminoantipyrine. HIV Nursing, 22(2), 2981-2993.

[50]. Sharma, S., et al. (2023). Synthesis, spectroscopic study, X-ray diffraction, and comparative antimicrobial study of Schiff bases. Journal of the Indian Chemical Society, 100(6), 100997.

[51]. Shahbahram, S. A., & Abdulkareem, I. I. (2023). New Schiff base ligand type [LH₂] donor derivative from 4-aminophenol. Zanco Journal of Pure and Applied Sciences, 35(1), 177-188.

[52]. Guo, L., et al. (2010). Preparation and characterization of chitosan poly(acrylic acid) magnetic microspheres. Marine Drugs, 8(7), 2212-2222.

[53]. Hanna, D. H., et al. (2023). Synthesis and characterization of poly(3-hydroxybutyrate)/chitosan-graft poly(acrylic acid) conjugate hyaluronate. International Journal of Biological Macromolecules, 240, 124396.

[54]. Wang, M., et al. (2021). A novel electrochemical sensor based on MWCNTs-COOH/metal-covalent organic frameworks. Microchemical Journal, 167, 106336.

[55]. Sedghi, R., & Pezeshkian, Z. (2015). Fabrication of non-enzymatic glucose sensor based on nanocomposite of MWCNTs-COOH-Poly(2-aminothiophenol)-Au NPs. Sensors and Actuators B: Chemical, 219, 119-124.

[56]. Merino G, Jonker JW, Wagenaar E, Pulido MM, Molina AJ, Alvarez AI, Schinkel AH. Transport of digoxin, a P-glycoprotein substrate, is modulated by multidrug resistance-associated proteins in mice. Drug Metab Dispos. 2005;33(5):614-618.

[57]. ygren P, Fryknäs M, Ågerup B, Larsson R. Repositioning of the anthelmintic drug mebendazole for the treatment of colon cancer. J Cancer Res Clin Oncol. 2013;139(12):2133-2140.

[58]. Adamson GW, Bawden D, Saggers DT. Computer-assisted substructure searching of pesticide chemical data: Evaluation of fragment coding methods. Pestic Sci. 1984;15(1):31-39.

[59]. Karam, F. F., & Kadhim, M. I. (2014). Determination of chrysene by gas chromatography in selected soils from Al-Diwaniya province, Iraq. Asian Journal of Chemistry, 26, S259-S261.

[60]. Al-Suraify, S. M. T. Synthesis and characterization of new heterocyclic compounds in corporating heterocyclic moiety derived from 3-chloro-1-methyl-1h-indazole. Biochemical and Cellular Archives 2020, 20, 4127-4134, Article. Scopus.

[61]. Al-Zuhairy, S. H.; Darweesh, M. A.; Othman, M. A. M. Relation of Serum Ferritin Level with Serum Hepcidin and Fucose Levels in Children with β-Thalassemia Major. Hemoglobin 2021, 45 (1), 69-73, Article. DOI: 10.1080/03630269.2021.1898419 Scopus.

[62]. Al-Hasan, H. A.; Munadi Th. Al-Suraify, S.; Othman, M. A. M.; Jasim, L. S.; Batool, M. Activated Nano-Carbon from Natural Sources for Water Treatment: A Comprehensive Review. Journal of Nanostructures 2025, 15 (3), 1443-1456, Article. DOI: 10.22052/JNS.2025.03.058 Scopus.

[63]. Al-Suraify, S. M. T. Synthesis and characterization of new heterocyclic compounds in corporating heterocyclic moiety derived from 3-chloro-1-methyl-1h-indazole. Biochemical and Cellular Archives 2020, 20, 4127-4134, Article. Scopus.

[64]. Bdaiwi, Z. M.; Abbas, G. J.; Ghanem, H. T. Synthesis, Characterization of Heterocyclic Compounds Containing Dapsone. International Journal of Drug Delivery Technology 2022, 12 (3), 1446-1452, Article. DOI: 10.25258/ijddt.12.3.87 Scopus.

[65]. Bdaiwi, Z. M.; Ghanem, H. T. Synthesis and characterization of some oxazepine compounds from 2- amino thiazole. Journal of Global Pharma Technology 2020, 12 (6), 291-303, Article. Scopus.

[66]. Bdaiwi, Z. M.; Ghanem, H. T. Synthesis and characterization of some heterocyclic derivatives from 2-amino thiazol and study of biological activity of prepared derivatives. International Journal of Pharmaceutical Research 2020, 12 (2), 1207-1216, Article. DOI: 10.31838/IJPR/2020.12.02.0181 Scopus.

[67]. Jamel, H. O.; Mwaea, M. S.; Eidan, D. M.; Mahdi, M. A.; Jasim, L. S. Synthesis, Characterization, and Biological Evaluation of Nano Schiff Base Metal Complexes: Antibacterial and Anticancer Potential Against Breast Cancer (MCF-7) Cells. Journal of Nanostructures 2025, 15 (1), 88-107, Article. DOI: 10.22052/JNS.2025.01.009 Scopus.

[68]. Jamel, H. O.; Ali, M. H.; Eidan, D. M.; Mahdi, M. A.; Jasim, L. S. Synthesis, Spectroscopic Characterization and Biological Studies as an Anticancer of a Novel Schiff Base Ligand (LH) and Its Palladium (II) Complex Derived from Thiazole and Salicylaldehyde. Journal of Nanostructures 2024, 14 (2), 466-480, Article. DOI: 10.22052/JNS.2024.02.009 Scopus.