Volume 9, Issue 3 (10-2021)
Jorjani Biomed J 2021, 9(3): 49-60 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Gharnas-ghamesh H, masoumi M, Erfani-moghadam V. Anticancer Activity of Doxorubicin Loaded PBMA-b-POEGMA Micelles against MCF7 Breast Cancer Cells and HepG2 Liver Cancer Cells. Jorjani Biomed J 2021; 9 (3) :49-60
URL: http://goums.ac.ir/jorjanijournal/article-1-847-en.html
URL: http://goums.ac.ir/jorjanijournal/article-1-847-en.html
1- Department of chemical engineering, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.
2- Department of chemical engineering, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran ,m.masoumi@iauamol.ac.ir
3- Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
2- Department of chemical engineering, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran ,
3- Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
Abstract: (4097 Views)
Background and Objective: Cancer is one of the most serious diseases. Doxorubicin is a type of chemotherapy drug used to treat a variety of cancers. Doxorubicin is a type of chemotherapy drug used to treat a variety of cancers. However, its side effects have limited its use. The aim of this study was to synthesize and evaluate polymer micelles containing doxorubicin and evaluate its toxicity on MCF7 breast cancer cells and HepG2 liver cancer cells.
Material and Methods: For this purpose, PBMA-b-POEGMA diblock copolymer was first synthesized using the RAFT method and confirmed by GPC. Dynamic light scattering (DLS) and Transmission electron microscope (TEM) were used to observe the morphology, size, and polydispersity of the micelles. In addition, in vitro cytotoxicity of DOX-loaded polymeric micelles against MCF7 cells and HepG2 cells were assessed. Furthermore, cell uptake and apoptosis assay of DOX-loaded polymeric micelles against MCF7 cells were evaluated.
Results: The TEM image revealed that the nanoparticles were spherical and uniform. The particle size and polydispersity measured by DLS were 35 nm and 0.13, respectively. The drug encapsulation efficiency and drug loading contents were 50±3.46 % and 4.53±0.29 %, respectively. The drug release rate was reported 69% in saline phosphate buffer (pH 7.4) within 24 hours. The results showed that micelles containing doxorubicin had a greater effect on MCF7 cell viability than the free drug. The MTT assay demonstrated that micelles were biocompatible to HepG2 cells while DOX-loaded micelles showed significant cytotoxicity. The IC50 of doxorubicin-loaded micelles against MCF7 cells were obtained to be 0.5 μg/ml. It was further shown that micelles containing doxorubicin had higher cell uptake and apoptosis than free drugs on MCF7 cells.
Material and Methods: For this purpose, PBMA-b-POEGMA diblock copolymer was first synthesized using the RAFT method and confirmed by GPC. Dynamic light scattering (DLS) and Transmission electron microscope (TEM) were used to observe the morphology, size, and polydispersity of the micelles. In addition, in vitro cytotoxicity of DOX-loaded polymeric micelles against MCF7 cells and HepG2 cells were assessed. Furthermore, cell uptake and apoptosis assay of DOX-loaded polymeric micelles against MCF7 cells were evaluated.
Results: The TEM image revealed that the nanoparticles were spherical and uniform. The particle size and polydispersity measured by DLS were 35 nm and 0.13, respectively. The drug encapsulation efficiency and drug loading contents were 50±3.46 % and 4.53±0.29 %, respectively. The drug release rate was reported 69% in saline phosphate buffer (pH 7.4) within 24 hours. The results showed that micelles containing doxorubicin had a greater effect on MCF7 cell viability than the free drug. The MTT assay demonstrated that micelles were biocompatible to HepG2 cells while DOX-loaded micelles showed significant cytotoxicity. The IC50 of doxorubicin-loaded micelles against MCF7 cells were obtained to be 0.5 μg/ml. It was further shown that micelles containing doxorubicin had higher cell uptake and apoptosis than free drugs on MCF7 cells.
Conclusion: These polymeric micelles are an ideal candidate to deliver anticancer agents into breast cancer cells.
Keywords: Micelles [MeSH], Doxorubicin [MeSH], Polymerization [MeSH], Drug Carriers [MeSH], MCF7 Cells [MeSH]
Type of Article: Original article |
Subject:
Molecular Sciences
Received: 2021/07/27 | Accepted: 2021/09/4 | Published: 2021/09/29
Received: 2021/07/27 | Accepted: 2021/09/4 | Published: 2021/09/29
References
1. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145. [view at publisher] [DOI] [PMID] [Google Scholar]
2. Shuai X, Ai H, Nasongkla N, Kim S, Gao J. Micellar carriers based on block copolymers of poly (ε-caprolactone) and poly (ethylene glycol) for doxorubicin delivery. J Control Release. 2004;98(3):415-26. [view at publisher] [DOI] [PMID] [Google Scholar]
3. Liu Y, Li L-L, Qi G-B, Chen X-G, Wang H. Dynamic disordering of liposomal cocktails and the spatio-temporal favorable release of cargoes to circumvent drug resistance. Biomaterials. 2014;35(10):3406-15. [view at publisher] [DOI] [PMID] [Google Scholar]
4. Chung M, Chen K, Liang H, Liao Z, Chia W, Xia Y, et al. A liposomal system capable of generating CO2 bubbles to induce transient cavitation, lysosomal rupturing, and cell necrosis. Angew Chemie Int Ed. 2012;51(40):10089-93. [view at publisher] [DOI] [PMID] [Google Scholar]
5. Han S, Liu Y, Nie X, Xu Q, Jiao F, Li W, et al. Efficient Delivery of Antitumor Drug to the Nuclei of Tumor Cells by Amphiphilic Biodegradable Poly (L‐Aspartic Acid‐co‐Lactic Acid)/DPPE Co‐Polymer Nanoparticles. Small. 2012;8(10):1596-606. [view at publisher] [DOI] [PMID] [Google Scholar]
6. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65(1):71-9. [view at publisher] [DOI] [PMID] [Google Scholar]
8. Burke SE, Eisenberg A. Kinetics and mechanisms of the sphere-to-rod and rod-to-sphere transitions in the ternary system PS310-b-PAA52/dioxane/water. Langmuir. 2001;17(21):6705-14. [view at publisher] [DOI] [Google Scholar]
9. Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46(12 Part 1):6387-92. [view at publisher] [Google Scholar]
10. Matsumura Y, Hamaguchi T, Ura T, Muro K, Yamada Y, Shimada Y, et al. Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br J Cancer. 2004;91(10):1775. [view at publisher] [DOI] [PMID] [PMCID] [Google Scholar]
11. Hwang D, Ramsey JD, Kabanov A V. Polymeric micelles for the delivery of poorly soluble drugs: from nanoformulation to clinical approval. Adv Drug Deliv Rev. 2020; [view at publisher] [DOI] [PMID] [Google Scholar]
12. Lin J, Peng C, Ravi S, Siddiki AKM, Zheng J, Balkus KJ. Biphenyl wrinkled mesoporous silica nanoparticles for pH-responsive doxorubicin drug delivery. Materials (Basel). 2020;13(8):1998. [view at publisher] [DOI] [PMID] [PMCID] [Google Scholar]
13. Gomaa EA, Morsi MA, Negm AE, Sherif YA. Cyclic voltammetry of bulk and nano manganese sulfate with Doxorubicin using glassy Carbon electrode. Int J Nano Dimens. 2017;8(1):89-96. [view at publisher] [Google Scholar]
14. Chen Y, Wan Y, Wang Y, Zhang H, Jiao Z. Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. Int J Nanomedicine. 2011;6:2321. [DOI] [PMID] [PMCID] [Google Scholar]
15. Cabeza L, Ortiz R, Arias JL, Prados J, Martínez MAR, Entrena JM, et al. Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly (butylcyanoacrylate) nanoparticles. Int J Nanomedicine. 2015;10:1291. [view at publisher] [DOI] [PMID] [PMCID] [Google Scholar]
16. He S, Zhou Z, Li L, Yang Q, Yang Y, Guan S, et al. Comparison of active and passive targeting of doxorubicin for somatostatin receptor 2 positive tumor models by octreotide-modified HPMA copolymer-doxorubicin conjugates. Drug Deliv. 2016;23(1):285-96. [view at publisher] [DOI] [PMID] [Google Scholar]
17. York AW, Kirkland SE, McCormick CL. Advances in the synthesis of amphiphilic block copolymers via RAFT polymerization: stimuli-responsive drug and gene delivery. Adv Drug Deliv Rev. 2008;60(9):1018-36. [view at publisher] [DOI] [PMID] [Google Scholar]
18. Jia Z, Wong L, Davis TP, Bulmus V. One-Pot Conversion of RAFT-Generated Multifunctional Block Copolymers of HPMA to Doxorubicin Conjugated Acid- and Reductant-Sensitive Crosslinked Micelles. 2008;3106-13. [view at publisher] [DOI] [PMID] [Google Scholar]
19. Boyer C, Bulmus V, Davis TP, Ladmiral V, Liu J, Perrier S. Bioapplications of RAFT polymerization. Chem Rev. 2009;109(11):5402-36. [view at publisher] [DOI] [PMID] [Google Scholar]
20. Khan M, Guimarães TR, Choong K, Moad G, Perrier S, Zetterlund PB. RAFT Emulsion Polymerization for (Multi) block Copolymer Synthesis: Overcoming the Constraints of Monomer Order. Macromolecules. 2021;54(2):736-46. [view at publisher] [DOI] [Google Scholar]
21. Du Y, Jia S, Chen Y, Zhang L, Tan J. Type I Photoinitiator-Functionalized Block Copolymer Nanoparticles Prepared by RAFT-Mediated Polymerization-Induced Self-Assembly. ACS Macro Lett. 2021;10(2):297-306. [view at publisher] [DOI] [Google Scholar]
22. Lo CL, Huang CK, Lin KM, Hsiue GH. Mixed micelles formed from graft and diblock copolymers for application in intracellular drug delivery. Biomaterials. 2007;28(6):1225-35. [view at publisher] [DOI] [PMID] [Google Scholar]
23. Ghorbani M, Mahmoodzadeh F, Nezhad-Mokhtari P, Hamishehkar H. A novel polymeric micelle-decorated Fe 3 O 4/Au core-shell nanoparticle for pH and reduction-responsive intracellular co-delivery of doxorubicin and 6-mercaptopurine. New J Chem. 2018;42(22):18038-49. [view at publisher] [DOI] [Google Scholar]
24. Guo X, Zhao Z, Chen D, Qiao M, Wan F, Cun D, et al. Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors. Asian J Pharm Sci. 2019;14(1):78-85. [view at publisher] [DOI] [PMID] [PMCID] [Google Scholar]
25. Li W, Nakayama M, Akimoto J, Okano T. Effect of block compositions of amphiphilic block copolymers on the physicochemical properties of polymeric micelles. Polymer (Guildf). 2011;52(17):3783-90. [view at publisher] [DOI] [Google Scholar]
26. Su X, Wang Z, Li L, Zheng M, Zheng C, Gong P, et al. Lipid-polymer nanoparticles encapsulating doxorubicin and 2′-deoxy-5-azacytidine enhance the sensitivity of cancer cells to chemical therapeutics. Mol Pharm. 2013;10(5):1901-9. [view at publisher] [DOI] [PMID] [Google Scholar]
27. Lv L, Liu C, Chen C, Yu X, Chen G, Shi Y, et al. Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer. Oncotarget. 2016;7(22):32184. [DOI] [PMID] [PMCID] [Google Scholar]
28. Masarudin MJ, Cutts SM, Evison BJ, Phillips DR, Pigram PJ. Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin. Nanotechnol Sci Appl. 2015;8:67. [DOI] [PMID] [PMCID] [Google Scholar]
29. Hazhir N, Chekin F, Raoof JB, Fathi S. A porous reduced graphene oxide/chitosan-based nanocarrier as a delivery system of doxorubicin. RSC Adv. 2019;9(53):30729-35. [view at publisher] [DOI] [Google Scholar]
30. Chekin F, Myshin V, Ye R, Melinte S, Singh SK, Kurungot S, et al. Graphene-modified electrodes for sensing doxorubicin hydrochloride in human plasma. Anal Bioanal Chem. 2019;411(8):1509-16. [view at publisher] [DOI] [PMID] [Google Scholar]
31. Hussein YHA, Youssry M. Polymeric micelles of biodegradable diblock copolymers: enhanced encapsulation of hydrophobic drugs. Materials (Basel). 2018;11(5):688. [view at publisher] [DOI] [PMID] [PMCID] [Google Scholar]
32. Hakemi P, Ghadi A, Mahjoub S, Zabihi E, Tashakkorian H. Ratio Design of Docetaxel/Quercetin Co-Loading-to-Nanocarrier: Synthesis of PCL-PEG-PCL Copolymer, Study of Drug Release Kinetic and Growth Inhibition of Human Breast Cancer (MCF-7) Cell Line. Russ J Appl Chem. 2021;94(3):388-401. [view at publisher] [DOI] [Google Scholar]
33. Phan QT, Le MH, Le TTH, Tran THH, Xuan PN, Ha PT. Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA: PEG ratios. Int J Pharm. 2016;507(1-2):32-40. [view at publisher] [DOI] [PMID] [Google Scholar]
34. Zhou Y, Wang S, Ying X, Wang Y, Geng P, Deng A, et al. Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer. Int J Nanomedicine. 2017;12:6153. [DOI] [PMID] [PMCID] [Google Scholar]
35. Cuong N-V, Jiang J-L, Li Y-L, Chen J-R, Jwo S-C, Hsieh M-F. Doxorubicin-loaded PEG-PCL-PEG micelle using xenograft model of nude mice: Effect of multiple administration of micelle on the suppression of human breast cancer. Cancers (Basel). 2011;3(1):61-78. [view at publisher] [DOI] [PMID] [PMCID] [Google Scholar]
36. Hong W, Shi H, Qiao M, Gao X, Yang J, Tian C, et al. Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells. Int J Nanomedicine. 2017;12:989. [view at publisher] [DOI] [PMID] [PMCID] [Google Scholar]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
