A Comparative Study of Synthesized Berberine-Iron Oxide Nanoparticles and Cisplatin: Characterization and Biological Applications
Abstract:
Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide due to its high incidence, aggressive progression, and limited treatment options. Although cisplatin-based chemotherapy is a standard treatment for NSCLC, its clinical use is hindered by severe side effects and drug resistance. To address these challenges, the present study focused on the green synthesis of berberine-loaded iron oxide nanoparticles (BBR-FeONPs) using Phyllanthus amarus as a natural reducing and stabilizing agent. The formation of BBR-FeONPs was indicated by a visible color change and confirmed through characterization techniques, including UV-visible spectroscopy, FTIR, XRD, SEM, TEM, and zeta potential analysis. UV-vis spectroscopy showed a surface plasmon resonance peak at 335-342 nm, while FTIR identified functional groups involved in nanoparticle stabilization. XRD confirmed their crystalline structure, and SEM/TEM analyses revealed spherical and oval-shaped particles with an average size of 52 ± 2 nm. Zeta potential analysis (-8.50 mV) indicated moderate colloidal stability. Antimicrobial assays showed dose-dependent inhibition zones against S. aureus (13.0 mm), E. coli (14.3 mm), and P. aeruginosa (15.0 mm). In vitro cytotoxicity studies demonstrated enhanced anticancer activity of BBR-FeONPs against H460 NSCLC cells (IC₅₀=34.27 ± 2 μg/mL) compared to BBR, FeONPs, and cisplatin, with lower toxicity toward HEK-293 normal cells. Wound healing assays showed significant anti-migratory activity (6.14% at 200 μg/mL). These findings suggest that BBR-FeONPs are a promising and safer alternative for NSCLC treatment. Further studies are needed to explore their molecular mechanisms, assess in vivo toxicity, and evaluate biodistribution profiles.References:
[1].
Bray F, Laversanne M,
Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer
statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36
cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63. https://doi.org/10.3322/caac.21709
[2].
Sathishkumar
K, Chaturvedi M, Das P, Stephen S, Mathur P. Cancer incidence estimates for
2022 and projection for 2025: Result from National Cancer Registry Programme,
India. Indian J Med Res. 2022;156(4):598-607.
[3].
Nath
A, Sathishkumar K, Das P, Sudarshan K, Mathur P. A clinic epidemiological
profile of lung cancers in India: Results from the National Cancer Registry
Programme. Indian J Med Res. 2022;155(2):264-72.
[4].
Malhotra
RK, Manoharan N, Nair O, Deo S, Rath GK. Trends in lung cancer incidence in
Delhi, India 1988-2012: Age-period-cohort and joinpoint analyses. Asian Pac J
Cancer Prev. 2018;19(6):1647-54.
[5].
Dela
Cruz CS, Tanoue LT, Matthay RA. Lung cancer: Epidemiology, etiology, and
prevention. Clin Chest Med. 2011;32:605-44. https://doi.org/10.1016/j.ccm.2011.09.001
[6].
Shankar
A, Dubey A, Saini D, Singh M, Prasad CP, Roy S, et al. Environmental and
occupational determinants of lung cancer. Transl Lung Cancer Res. 2019;8(Suppl
1):S31-49. https://doi.org/10.21037/tlcr.2019.03.11
[7].
Wangmu
T, Li C, Han G, Yi P. Berberine restrained proliferation, invasion, and
migration by targeting the glycogen synthase kinase 3β/β-catenin pathway in
lung adenocarcinoma cells. Oncol Transl Med. 2025. [In press].
[8].
Patra JK, Das G,
Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug
delivery systems: Recent developments and future prospects. J Nanobiotechnol.
2018;16:71. https://doi.org/10.1186/s12951-018-0392-8
[9].
Su Z, Dong S, Zhao
SC, Liu K, Tan Y, Jiang X, et al. Novel nanomedicines to overcome cancer
multidrug resistance. Drug Resist Updat. 2021;58:100777. https://doi.org/10.1016/j.drup.2021.100777
[10]. Madani M, Hosny S,
Alshangiti DM, Nady N, Alkhursani SA, Alkhaldi H, et al. Green synthesis of
nanoparticles for varied applications: Green renewable resources and
energy-efficient synthetic routes. Nanotechnol Rev. 2022;11(1):731-59. https://doi.org/10.1515/ntrev-2022-0063
[11]. Patel JR, Tripathi P, Sharma V, Chauhan NS, Dixit VK. Phyllanthus
amarus: Ethnomedicinal uses, phytochemistry and pharmacology: A review. J
Ethnopharmacol. 2011;138:286-313. https://doi.org/10.1016/j.jep.2011.09.040
[12]. Thatyana M, Dube
NP, Kemboi D, Manicum ALE, Mokgalaka-Fleischmann NS, Tembu JV. Advances in
phytonanotechnology: A plant-mediated green synthesis of metal nanoparticles
using Phyllanthus plant extracts and their antimicrobial and anticancer
applications. Nanomaterials. 2023;13(1):176. https://doi.org/10.3390/nano13010176
[13]. Samuel MS,
Ravikumar M, John A, Selvarajan E, Patel H, Chander PS, et al. A review on
green synthesis of nanoparticles and their diverse biomedical and environmental
applications. Catalysts. 2022;12(7):718. https://doi.org/10.3390/catal12070718
[14]. Iqbal MJ, Quispe C, Javed Z, Sadia H, Qadri QR, Raza S, et al. Nanotechnology-based
strategies for berberine delivery system in cancer treatment: Pulling strings
to keep berberine in power. Front Mol Biosci. 2021;7:624494. https://doi.org/10.3389/fmolb.2020.624494
[15]. Kumar A, Ekavali,
Chopra K, Mukherjee M, Pottabathini R, Dhull DK. Current knowledge and
pharmacological profile of berberine: An update. Eur J Pharmacol.
2015;761:288-97. https://doi.org/10.1016/j.ejphar.2015.05.068
[16]. Mehra M, Sheorain
J, Bakshi J, Thakur R, Grewal S, Dhingra D, et al. Synthesis and evaluation of
berberine loaded chitosan nanocarrier for enhanced in-vitro antioxidant and
anti-inflammatory potential. Carbohydr Polym Technol Appl. 2024;7:100326.
[17]. Dasari S,
Tchounwou PB. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur
J Pharmacol. 2014;740:364-78. https://doi.org/10.1016/j.ejphar.2014.07.025
[18]. Devarajan N, Manjunathan R, Ganesan SK. Tumor hypoxia: The major culprit behind
cisplatin resistance in cancer patients. Crit Rev Oncol Hematol.
2021;162:103327. https://doi.org/10.1016/j.critrevonc.2021.103327
[19]. Tarawneh N,
Hamadneh L, Abu-Irmaileh B, Shraideh Z, Bustanji Y, Abdalla S, et al. Berberine
inhibited growth and migration of human colon cancer cell lines by increasing
phosphatase and tensin and inhibiting aquaporins 1, 3 and 5 expressions.
Molecules. 2023;28(9):3823. https://doi.org/10.3390/molecules28093823
[20]. Ravi L, Jain P,
Maddali V, Madhushree SH, Kajagar S, Doodi S, et al. Green synthesized
heteromorphic iron oxide nanoparticles (Fe₃O₄NPs) as potential food additive,
food supplement and food colorant sensor and their physiological impact on Drosophila
melanogaster. Discov Appl Sci. 2025;7(4):225. https://doi.org/10.1007/s42452-025-06592-3
[21]. Minhas LA, Kaleem M, Minhas MAH, Waqar R, Al Farraj DA, Alsaigh MA, et al. Biogenic
fabrication of iron oxide nanoparticles from Leptolyngbya sp. L-2 and
multiple in vitro pharmacogenetic properties. Toxics. 2023;11(7).
[22]. Soetaert F,
Korangath P, Serantes D, Fiering S, Ivkov R. Cancer therapy with iron oxide
nanoparticles: Agents of thermal and immune therapies. Adv Drug Deliv Rev.
2020;163-164:65-83. https://doi.org/10.1016/j.addr.2020.05.010
[23]. Shestovskaya MV, Luss AL, Bezborodova OA, Makarov VV, Keskinov AA. Iron oxide
nanoparticles in cancer treatment: Cell responses and the potency to improve
radiosensitivity. Pharmaceutics. 2023;15(4). https://doi.org/10.3390/pharmaceutics15041021
[24]. Kheir MM, Wang Y, Hua L, Hu J, Li L, Lei F, et al. Acute toxicity of
berberine and its correlation with the blood concentration in mice. Food Chem
Toxicol. 2010;48(4):1105-10. https://doi.org/10.1016/j.fct.2010.01.023
[25]. Hasan E, Manzar Z,
Haroon N, Raza A, Ali SN, Lateef M, et al. A facile synthesis of iron oxide
nanoparticles as a nano-sensor to detect levofloxacin and ciprofloxacin in
human blood and evaluation of their biological activities. RSC Adv.
2024;14(48):36093-100.
[26]. Aisida SO,
Madubuonu N, Alnasir MH, Ahmad I, Botha S, Maaza M, et al. Biogenic synthesis
of iron oxide nanorods using Moringa oleifera leaf extract for
antibacterial applications. Appl Nanosci. 2020;10(1):305-15.
[27]. Nguyen HT, Pham
TN, Le AT, Thuy NT, Huy TQ, Nguyen TTT. Antibacterial activity of a berberine
nanoformulation. Beilstein J Nanotechnol. 2022;13:641-52. https://doi.org/10.3762/bjnano.13.57
[28]. Liu X, Wang J,
Chen B, Niu B, Li J. Preparation of berberine magnetic nanoparticles and their
inhibition of human gastric cancer BGC-823 cells. AIP Adv. 2024;14(1). https://doi.org/10.1063/5.0123456
[29]. Manzoor N, Ahmed
T, Noman M, Shahid M, Nazir MM, Ali L, et al. Iron oxide nanoparticles
ameliorated the cadmium and salinity stresses in wheat plants, facilitating
photosynthetic pigments and restricting cadmium uptake. Sci Total Environ.
2021;769. https://doi.org/10.1016/j.scitotenv.2020.144466
[30]. Rasheed R, Meera
V. Synthesis of iron oxide nanoparticles coated sand by biological method and
chemical method. Procedia Technol. 2016;24:210-16. https://doi.org/10.1016/j.protcy.2016.05.030
[31]. Singh K, Chopra
DS, Singh D, Singh N. Optimization and ecofriendly synthesis of iron oxide
nanoparticles as potential antioxidant. Arab J Chem. 2020;13(12):9034-46. https://doi.org/10.1016/j.arabjc.2020.07.002
[32]. Osman AI, Zhang Y,
Farghali M, Rashwan AK, Eltaweil AS, Abd El-Monaem EM, et al. Synthesis of
green nanoparticles for energy, biomedical, environmental, agricultural, and
food applications: A review. Environ Chem Lett. 2024;22:841-87.
[33]. Antunes Filho S, dos Santos MS, dos Santos OAL, Backx BP, Soran ML, Opriş
O, et al. Biosynthesis
of nanoparticles using plant extracts and essential oils. Molecules.
2023;28(1):1234.
[34]. Chen QQ, Shi JM,
Ding Z, Xia Q, Zheng TS, Ren YB, et al. Berberine induces apoptosis in
non-small-cell lung cancer cells by upregulating miR-19a targeting tissue
factor. Cancer Manag Res. 2019;11:9005-15.
[35]. Bharathi D,
Preethi S, Abarna K, Nithyasri M, Kishore P, Deepika K. Bio-inspired synthesis
of flower-shaped iron oxide nanoparticles (FeONPs) using phytochemicals of Solanum
lycopersicum leaf extract for biomedical applications. Biocatal Agric
Biotechnol. 2020;27:101689. https://doi.org/10.1016/j.bcab.2020.101689
[36]. Madhulatha AVS,
Darwin CR. Berberine loaded magnetic nanoparticles for breast cancer therapy on
MDA-MB-231 cell lines. Asian J Chem. 2022;34(8):2147-54. https://doi.org/10.14233/ajchem.2022.23784
[37]. Aleissa MS,
Al-Zharani M, Alneghery LM, Aleissa AM. Berberine enhances the sensitivity of
radiotherapy in ovarian cancer cell line (SKOV-3). Saudi Pharm J.
2023;31(1):110-18. https://doi.org/10.1016/j.jsps.2022.11.006
[38]. Waly MI, Al
Moundhri MS, Ali BH. Effect of curcumin on cisplatin- and oxaliplatin-induced
oxidative stress in human embryonic kidney (HEK) 293 cells. Ren Fail.
2011;33(5):518-23.
[39]. Huang C, Liu H, Yang Y, He Y, Shen W. Berberine suppressed the epithelial-mesenchymal transition (EMT) of colon epithelial cells through the TGF-β1/Smad and NF-κB pathways associated with miRNA-1269a. Heliyon. 2024;10(16):e28194. https://doi.org/10.1016/j.heliyon.2024.e28194
