Skip to main content
Log in

Synergic Fabrication of Naringin Molecule into Polymeric Nanoparticles for the Treatment and Nursing Care of Lung Cancer Therapy

  • Original Paper
  • Published:
Journal of Polymers and the Environment Aims and scope Submit manuscript

Abstract

Lung cancer is the third most common cause of death and the main factor of cancer-related deaths in both males and females in the United States to the rest of the world. Diagnosis at an important level is associated with high mortality in the population of cases. Herein, we present a very easy and cost-effective method that incorporates drugs reconstruction, tumor-specific targeting supramolecular nanoassembly, and therapeutically to overcome the different challenges raised by the distribution of the pharmaceutical potential anticancer drug Naringin. On covalent conjugations of hydrophobic linoleic acid by hydroxyl group, the Naringin prodrugs were skilled in impulsively nanoassembly into extremely steady nanoparticles size (~ 100 nm). Electron microscopic techniques have verified the newly synthesized morphology of Naringin-NPs. The anticancer properties of Naringin and Naringin-NPs against A549 and HEL-299 (lung carcinoma) cancer cell lines have been evaluated after successful synthesis. Other research, such as dual staining acridine orange/ethidium bromide, Hoechst 33,344 and flow cytometry study on the apoptosis mechanisms have shown that proliferation in lung cancer cells is associated with apoptosis. Compared to Naringin, Naringin-NPs demonstrate excellent biocompatibility, this study clarified the Naringin-NPs as a healthy and positive lung cancer treatment and care chemotherapeutics technique and deserve further clinical evaluations.

Graphic Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ghosh S, Lalani R, Maiti K, Banerjee S, Bhatt H, Bobde YS, Patel V, Biswas S, Bhowmick S, Misra A (2021) Synergistic co-loading of vincristine improved chemotherapeutic potential of pegylated liposomal doxorubicin against triple negative breast cancer and non-small cell lung cancer. Nanomed Nanotechnol Biol Med 31:102320. https://doi.org/10.1016/j.nano.2020.102320

    Article  CAS  Google Scholar 

  2. Novoselova MV, Loh HM, Trushina DB, Ketkar A, Abakumova TO, Zatsepin TS, Kakran M, Brzozowska AM, Lau HH, Gorin DA, Antipina MN, Brichkina AI (2020) Biodegradable polymeric multilayer capsules for therapy of lung cancer. ACS Appl Mater Interfaces 12:5610–5623. https://doi.org/10.1021/acsami.9b21381

    Article  CAS  PubMed  Google Scholar 

  3. Abdelaziz HM, Elzoghby AO, Helmy MW, Abdelfattah E-ZA, Fang J-Y, Samaha MW, Freag MS (2020) Inhalable lactoferrin/chondroitin-functionalized monoolein nanocomposites for localized lung cancer targeting. ACS Biomater Sci Eng 6:1030–1042. https://doi.org/10.1021/acsbiomaterials.9b01639

    Article  CAS  PubMed  Google Scholar 

  4. Xie X, Li Y, Zhao D, Fang C, He D, Yang Q, Yang L, Chen R, Tan Q, Zhang J (2020) Oral administration of natural polyphenol-loaded natural polysaccharide-cloaked lipidic nanocarriers to improve efficacy against small-cell lung cancer. Nanomed Nanotechnol Biol Med 29:102261. https://doi.org/10.1016/j.nano.2020.102261

    Article  CAS  Google Scholar 

  5. Guan X, Yang B, Xie M, Ban DK, Zhao X, Lal R, Zhang F (2019) MRI reporter gene MagA suppresses transferrin receptor and maps Fe2 + dependent lung cancer. Nanomed Nanotechnol Biol Med 21:102064. https://doi.org/10.1016/j.nano.2019.102064

    Article  CAS  Google Scholar 

  6. Chen Y, Sun J, Huang Y, Liu Y, Liang L, Yang D, Lu B, Li S (2019) Targeted codelivery of doxorubicin and IL-36γ expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis. Nanomed Nanotechnol Biol Med 15:129–141. https://doi.org/10.1016/j.nano.2018.09.005

    Article  CAS  Google Scholar 

  7. Zhang L, Li J, Hao C, Guo W, Wang D, Zhang J, Zhao Y, Duan S, Yao W (2018) Up-regulation of exosomal miR-125a in pneumoconiosis inhibits lung cancer development by suppressing expressions of EZH2 and hnRNPK. RSC Adv 8:26538–26548. https://doi.org/10.1039/C8RA03081B

    Article  CAS  PubMed Central  Google Scholar 

  8. Amreddy N, Babu A, Panneerselvam J, Srivastava A, Muralidharan R, Chen A, Zhao YD, Munshi A, Ramesh R (2018) Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment. Nanomed Nanotechnol Biol Med 14:373–384. https://doi.org/10.1016/j.nano.2017.11.010

    Article  CAS  Google Scholar 

  9. Zhang C, Li C, Xu Y, Feng L, Shang D, Yang X, Han J, Sun Z, Li Y, Li X (2015) Integrative analysis of lung development–cancer expression associations reveals the roles of signatures with inverse expression patterns. Mol Biosyst 11:1271–1284. https://doi.org/10.1039/C5MB00061K

    Article  CAS  PubMed  Google Scholar 

  10. Liu Z, Ma L, Wen Z-S, Cheng Y-X, Zhou G-B (2014) Ethoxysanguinarine induces inhibitory effects and downregulates CIP2A in lung cancer cells. ACS Med Chem Lett 5:113–118. https://doi.org/10.1021/ml400341k

    Article  CAS  PubMed  Google Scholar 

  11. Chen Q, Jiao D, Wu Y, Wang L, Hu H, Song J, Yan J, Wu L (2013) Functional and pathway enrichment analysis for integrated regulatory network of high- and low-metastatic lung cancer. Mol Biosyst 9:3080–3090. https://doi.org/10.1039/C3MB70288J

    Article  CAS  PubMed  Google Scholar 

  12. Sung H-J, Ahn J-M, Yoon Y-H, Rhim T-Y, Park C-S, Park J-Y, Lee S-Y, Kim J-W, Cho J-Y (2011) Identification and validation of SAA as a potential lung cancer biomarker and its involvement in metastatic pathogenesis of lung cancer. J Proteome Res 10:1383–1395. https://doi.org/10.1021/pr101154j

    Article  CAS  PubMed  Google Scholar 

  13. Wu Y, Crawford M, Yu B, Mao Y, Nana-Sinkam SP, Lee LJ (2011) MicroRNA delivery by cationic lipoplexes for lung cancer therapy. Mol Pharm 8:1381–1389. https://doi.org/10.1021/mp2002076

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Keller A, Backes C, Leidinger P, Kefer N, Boisguerin V, Barbacioru C, Vogel B, Matzas M, Huwer H, Katus HA, Stähler C, Meder B, Meese E (2011) Next-generation sequencing identifies novel microRNAs in peripheral blood of lung cancer patients. Mol BioSyst 7:3187–3199. https://doi.org/10.1039/C1MB05353A

    Article  CAS  PubMed  Google Scholar 

  15. Magee ND, Villaumie JS, Marple ET, Ennis M, Elborn JS, McGarvey JJ (2009) Ex vivo diagnosis of lung cancer using a raman miniprobe. J Phys Chem B 113:8137–8141. https://doi.org/10.1021/jp900379w

    Article  CAS  PubMed  Google Scholar 

  16. Park H-J, Kim B-G, Lee S-J, Heo S-H, Kim J-Y, Kwon T-H, Lee E-B, Ryoo H-M, Cho J-Y (2008) Proteomic profiling of endothelial cells in human lung cancer. J Proteome Res 7:1138–1150. https://doi.org/10.1021/pr7007237

    Article  CAS  PubMed  Google Scholar 

  17. Li P, Wu H, Wang Y, Peng W, Su W (2020) Toxicological evaluation of naringin: acute, subchronic, and chronic toxicity in Beagle dogs. Regul Toxicol Pharmacol 111:104580. https://doi.org/10.1016/j.yrtph.2020.104580

    Article  CAS  PubMed  Google Scholar 

  18. Gollavilli H, Hegde AR, Managuli RS, Bhaskar KV, Dengale SJ, Reddy MS, Kalthur G, Mutalik S (2020) Naringin nano-ethosomal novel sunscreen creams: development and performance evaluation. Colloids Surfaces B Biointerfaces 193:111122. https://doi.org/10.1016/j.colsurfb.2020.111122

    Article  CAS  PubMed  Google Scholar 

  19. Syed AA, Reza MI, Shafiq M, Kumariya S, Singh P, Husain A, Hanif K, Gayen JR (2020) Naringin ameliorates type 2 diabetes mellitus-induced steatohepatitis by inhibiting RAGE/NF-κB mediated mitochondrial apoptosis. Life Sci 257:118118. https://doi.org/10.1016/j.lfs.2020.118118

    Article  CAS  PubMed  Google Scholar 

  20. Gerçek E, Zengin H, Erdem Erişir F, Yılmaz Ö (2021) Biochemical changes and antioxidant capacity of naringin and naringenin against malathion toxicity in Saccharomyces cerevisiae. Comp Biochem Physiol Part C Toxicol Pharmacol 241:108969. https://doi.org/10.1016/j.cbpc.2020.108969

    Article  CAS  Google Scholar 

  21. Guo X, Li K, Guo A, Li E (2020) Intestinal absorption and distribution of naringin, hesperidin, and their metabolites in mice. J Funct Foods 74:104158. https://doi.org/10.1016/j.jff.2020.104158

    Article  CAS  Google Scholar 

  22. Ni K, Guo J, Bu B, Pan Y, Li J, Liu L, Luo M, Deng L (2021) Naringin as a plant-derived bitter tastant promotes proliferation of cultured human airway epithelial cells via activation of TAS2R signaling. Phytomedicine. 84:153491. https://doi.org/10.1016/j.phymed.2021.153491

    Article  CAS  PubMed  Google Scholar 

  23. Tang X, Zhao H, Jiang W, Zhang S, Guo S, Gao X, Yang P, Shi L, Liu L (2018) Pharmacokinetics and pharmacodynamics of citrus peel extract in lipopolysaccharide-induced acute lung injury combined with Pinelliae Rhizoma Praeparatum. Food Funct 9:5880–5890. https://doi.org/10.1039/C8FO01337C

    Article  CAS  PubMed  Google Scholar 

  24. Dai H, Yang C, Ma X, Lin Y, Chen G (2011) A highly sensitive and selective sensing ECL platform for naringin based on β-Cyclodextrin functionalized carbon nanohorns. Chem Commun 47:11915–11917. https://doi.org/10.1039/C1CC14611D

    Article  CAS  Google Scholar 

  25. Feng X, Wu T, Yu B, Wang Y, Zhong S (2017) Hydrophilic surface molecularly imprinted naringin prepared via reverse atom transfer radical polymerization with excellent recognition ability in a pure aqueous phase. RSC Adv 7:28082–28091. https://doi.org/10.1039/C7RA00202E

    Article  CAS  Google Scholar 

  26. Jabbari M, Khosravi N, Feizabadi M, Ajloo D (2017) Solubility temperature and solvent dependence and preferential solvation of citrus flavonoid naringin in aqueous DMSO mixtures: an experimental and molecular dynamics simulation study. RSC Adv 7:14776–14789. https://doi.org/10.1039/C7RA00038C

    Article  CAS  Google Scholar 

  27. Selvaraj S, Krishnaswamy S, Devashya V, Sethuraman S, Krishnan UM (2014) Investigations on the membrane interactions of naringin and its complexes with copper and iron: implications for their cytotoxicity. RSC Adv 4:46407–46417. https://doi.org/10.1039/C4RA08157A

    Article  CAS  Google Scholar 

  28. Mandial D, Khullar P, Kumar H, Ahluwalia GK, Bakshi MS (2018) Naringin–chalcone bioflavonoid-protected nanocolloids: mode of flavonoid adsorption, a determinant for protein extraction. ACS Omega 3:15606–15614. https://doi.org/10.1021/acsomega.8b01776

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Memariani Z, Abbas SQ, ul Hassan SS, Ahmadi A, Chabra A (2020) Naringin and naringeninin as anticancer agents and adjuvants in cancer combination therapy; efficacy and molecular mechanisms of action, a comprehensive narrative review. Pharmacol Res 10:5264. https://doi.org/10.1016/j.phrs.2020.105264

    Article  Google Scholar 

  30. Albayrak D, Doğanlar O, Erdoğan S, Meraklı M, Doğan A, Turker P, Bostancı A, Doğanlar ZB (2021) Naringin combined with NF-κB inhibition and endoplasmic reticulum stress induces apoptotic cell death via oxidative stress and the PERK/eIF2α/ATF4/CHOP Axis in HT29 colon cancer cells. Biochem Genet 59:159–184. https://doi.org/10.1007/s10528-020-09996-5

    Article  CAS  PubMed  Google Scholar 

  31. Shao Y, You D, Lou Y, Li J, Ying B, Cheng K, Weng W, Wang H, Yu M, Dong L (2019) Controlled Release of Naringin in GelMA-Incorporated Rutile Nanorod Films to Regulate Osteogenic Differentiation of Mesenchymal Stem Cells. ACS Omega 4:19350–19357. https://doi.org/10.1021/acsomega.9b02751

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Yu M, You D, Zhuang J, Lin S, Dong L, Weng S, Zhang B, Cheng K, Weng W, Wang H (2017) Controlled Release of Naringin in Metal-Organic Framework-Loaded Mineralized Collagen Coating to Simultaneously Enhance Osseointegration and Antibacterial Activity. ACS Appl Mater Interfaces 9:19698–19705. https://doi.org/10.1021/acsami.7b05296

    Article  CAS  PubMed  Google Scholar 

  33. Wang F, Zhao C, Tian G, Wei X, Ma Z, Cui J, Wei R, Bao Y, Kong W, Zheng J (2020) Naringin Alleviates Atherosclerosis in ApoE–/– Mice by Regulating Cholesterol Metabolism Involved in Gut Microbiota Remodeling. J Agric Food Chem 68:12651–12660. https://doi.org/10.1021/acs.jafc.0c05800

    Article  CAS  PubMed  Google Scholar 

  34. Cao H, Liu J, Shen P, Cai J, Han Y, Zhu K, Fu Y, Zhang N, Zhang Z, Cao Y (2018) Protective Effect of Naringin on DSS-Induced Ulcerative Colitis in Mice. J Agric Food Chem 66:13133–13140. https://doi.org/10.1021/acs.jafc.8b03942

    Article  CAS  PubMed  Google Scholar 

  35. Zeng X, Yao H, Zheng Y, Chen T, Peng W, Wu H, Su W (2020) Metabolite Profiling of Naringin in Rat Urine and Feces Using Stable Isotope-Labeling-Based Liquid Chromatography-Mass Spectrometry. J Agric Food Chem 68:409–417. https://doi.org/10.1021/acs.jafc.9b06494

    Article  CAS  PubMed  Google Scholar 

  36. Ding D, Li K, Zhu Z, Pu KY, Hu Y, Jiang X, Liu B (2011) Conjugated polyelectrolyte-cisplatin complex nanoparticles for simultaneous in vivo imaging and drug tracking. Nanoscale 3:1997–2002. https://doi.org/10.1039/c0nr00950d

    Article  CAS  PubMed  Google Scholar 

  37. Huang Y, He Y, Huang Z, Jiang Y, Chu W, Sun X, Huang L, Zhao C (2017) Coordination self-assembly of platinum-bisphosphonate polymer-metal complex nanoparticles for cisplatin delivery and effective cancer therapy. Nanoscale 9:10002–10019. https://doi.org/10.1039/c7nr02662e

    Article  CAS  PubMed  Google Scholar 

  38. Han W, Shi L, Ren L, Zhou L, Li T, Qiao Y, Wang H (2018) A nanomedicine approach enables co-delivery of cyclosporin A and gefitinib to potentiate the therapeutic efficacy in drug-resistant lung cancer, Signal Transduct. Target Ther 3:1–10. https://doi.org/10.1038/s41392-018-0019-4

    Article  CAS  Google Scholar 

  39. Balaji S, Mohamed Subarkhan MK, Ramesh R, Wang H, Semeril D (2020) Synthesis and Structure of Arene Ru(II) N∧O-Chelating Complexes: In Vitro Cytotoxicity and Cancer Cell Death Mechanism. Organometallics 39:1366–1375. https://doi.org/10.1021/acs.organomet.0c00092

    Article  CAS  Google Scholar 

  40. Llinàs MC, Martínez-Edo G, Cascante A, Porcar I, Borrós S, Sánchez-García D (2018) Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT ph-triggered delivery. Drug Deliv 25:1137–1146. https://doi.org/10.1080/10717544.2018.1472678

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Tambe P, Kumar P, Paknikar KM, Gajbhiye V (2018) Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells. Int J Nanomedicine 13:7669–7680. https://doi.org/10.2147/IJN.S184634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Deng B, Ma P, Xie Y (2015) Reduction-sensitive polymeric nanocarriers in cancer therapy: a comprehensive review. Nanoscale 7:12773–12795. https://doi.org/10.1039/c5nr02878g

    Article  CAS  PubMed  Google Scholar 

  43. Mohamed Subarkhan MK, Ramesh R, Liu Y (2016) Synthesis and molecular structure of arene ruthenium(ii) benzhydrazone complexes: impact of substitution at the chelating ligand and arene moiety on antiproliferative activity. New J Chem 40:9813–9823. https://doi.org/10.1039/C6NJ01936F

    Article  CAS  Google Scholar 

  44. Li X, Gao Y (2020) Synergistically fabricated polymeric nanoparticles featuring dual drug delivery system to enhance the nursing care of cervical cancer. Process Biochem 98:254–261. https://doi.org/10.1016/j.procbio.2020.09.010

    Article  CAS  Google Scholar 

  45. Kasibhatla S, Amarante-Mendes GP, Finucane D, Brunner T, Bossy-Wetzel E, Green DR (2006) Acridine orange/ethidium bromide (AO/EB) staining to detect apoptosis. CSH Protoc. https://doi.org/10.1101/pdb.prot4493

  46. Mohamed Kasim MS, Sundar S, Rengan R (2018) Synthesis and structure of new binuclear ruthenium(ii) arene benzil bis(benzoylhydrazone) complexes: investigation on antiproliferative activity and apoptosis induction. Inorg Chem Front 5:585–596. https://doi.org/10.1039/C7QI00761B

    Article  CAS  Google Scholar 

  47. Zhang W-Y, Wang Y-J, Du F, He M, Gu Y-Y, Bai L, Yang L-L, Liu Y-J (2019) Evaluation of anticancer effect in vitro and in vivo of iridium(III) complexes on gastric carcinoma SGC-7901 cells. Eur J Med Chem 178:401–416. https://doi.org/10.1016/j.ejmech.2019.06.003

    Article  CAS  PubMed  Google Scholar 

  48. Subarkhan MKM, Ramesh R (2016) Ruthenium(II) arene complexes containing benzhydrazone ligands: synthesis, structure and antiproliferative activity. Inorganic Chem Front 3:1245–1255. https://doi.org/10.1039/c6qi00197a

    Article  CAS  Google Scholar 

  49. Sathiya Kamatchi T, Mohamed Subarkhan MK, Ramesh R, Wang H, Małecki JG (2020) Investigation into antiproliferative activity and apoptosis mechanism of new arene Ru(ii) carbazole-based hydrazone complexes. Dalt Trans 49:11385–11395. https://doi.org/10.1039/D0DT01476A

    Article  CAS  Google Scholar 

  50. Pragathiswaran C, Smitha C, Barabadi H, Al-Ansari MM, Al-Humaid LA, Saravanan M (2020) TiO2@ZnO nanocomposites decorated with gold nanoparticles: synthesis, characterization and their antifungal, antibacterial, anti-inflammatory and anticancer activities. Inorg Chem Commun 121:108210. https://doi.org/10.1016/j.inoche.2020.108210

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mindan Xie.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yan, L., Chen, H. & Xie, M. Synergic Fabrication of Naringin Molecule into Polymeric Nanoparticles for the Treatment and Nursing Care of Lung Cancer Therapy. J Polym Environ 29, 4048–4059 (2021). https://doi.org/10.1007/s10924-021-02151-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10924-021-02151-0

Keywords

Navigation