Abstract
Recent attention on chemotherapy against cancer is to explore the effective therapy through targeted delivery of anticancer agents to the tumor site by manipulating pharmacokinetic properties of nanocarriers. 5-Fluorouracil (5-FU) and curcumin (CUR) loaded chitosan/reduced graphene oxide (CS/rGO) nanocomposite has been prepared via simple chemical method. The polymer matrix-type chitosan/rGO nanocomposite, before and after encapsulation, has been analyzed by various characterizations. Entrapment and loading efficiencies were estimated. The results that demonstrated higher entrapment efficiency (> 90%) were achieved by CS/rGO nanocarrier. Various kinetic models were used to analyze the release model and to elucidate the release mechanism of the drug from CS/rGO nanocomposite. The synergistic cytotoxicity was observed on addition of 5-FU + CUR-loaded CS/rGO nanocomposite which shows the effectiveness of the system toward the inhibition of growth of HT-29 colon cancer cells. The better cytotoxicity with an IC50 of 23.8 μg/mL was observed for dual-drug-loaded nanocomposite.
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Jemal A, Center MM, DeSantis C, Ward EM (2010) Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomark Prev 19:1893–1907
Xiao W, Zeng X, Lin H, Han K, Jia H-Z, Zhang X-Z (2015) Dual stimuli-responsive multi-drug delivery system for the individually controlled release of anti-cancer drugs. Chem Commun 51:1475–1478
Li J-L, Jiang L, Wang B-W, Tian J-L, Gu W, Liu X, Yan S-P (2015) Significant differences in the biological activity of mononuclear Cu(ii) and Ni(ii) complexes with the polyquinolinyl ligand. New J Chem 39:529–538
Thomas Boyle F, Costello GF (1998) Cancer therapy: a move to the molecular level. Chem Soc Rev 27:251–261
Seyed MA, Jantan I, Bukhari SNA, Vijayaraghavan K (2016) A comprehensive review on the chemotherapeutic potential of piceatannol for cancer treatment, with mechanistic insights. J Agric Food Chem 64:725–737
Chen S-L (2017) Review of laser-generated ultrasound transmitters and their applications to all-optical ultrasound transducers and imaging. Appl Sci 7:25
Tran TH, Nguyen HT, Pham TT, Choi JY, Choi H-G, Yong CS, Kim JO (2015) Development of a graphene oxide nanocarrier for dual-drug chemo-phototherapy to overcome drug resistance in cancer. ACS Appl Mater Interfaces 7:28647–28655
Hess U, Shahabi S, Treccani L, Streckbein P, Heiss C, Rezwan K (2017) Co-delivery of cisplatin and doxorubicin from calcium phosphate beads/matrix scaffolds for osteosarcoma therapy. Mater Sci Eng C 77:427–435
Guo X, Zhao Z, Chen D, Qiao M, Wan F, Cun D, Sun Y, Yang M (2019) Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors. Asian J Pharm Sci 14:78–85
Nivethaa EAK, Dhanavel S, Narayanan V, Vasu CA, Stephen A (2015) An in vitro cytotoxicity study of 5-fluorouracil encapsulated chitosan/gold nanocomposites towards MCF-7 cells. RSC Adv 5:1024–1032
Gao P, Liu M, Tian J, Deng F, Wang K, Xu D, Liu L, Zhang X, Wei Y (2016) Improving the drug delivery characteristics of graphene oxide based polymer nanocomposites through the “one-pot” synthetic approach of single-electron-transfer living radical polymerization. Appl Surf Sci 378:22–29
Li C, Zhuang Z, Jin X, Chen Z (2017) A facile and green preparation of reduced graphene oxide using Eucalyptus leaf extract. Appl Surf Sci 422:469–474
Zhang B, Yan Y, Shen Q, Ma D, Huang L, Cai X, Tan S (2017) A colon targeted drug delivery system based on alginate modificated graphene oxide for colorectal liver metastasis. Mater Sci Eng C 79:185–190
Wang G, Ma Y, Zhang L, Mu J, Zhang Z, Zhang X, Che H, Bai Y, Hou J (2016) Facile synthesis of manganese ferrite/graphene oxide nanocomposites for controlled targeted drug delivery. J Magn Magn Mater 401:647–650
Hussien NA, Işıklan N, Türk M (2018) Aptamer-functionalized magnetic graphene oxide nanocarrier for targeted drug delivery of paclitaxel. Mater Chem Phys 211:479–488
Ma N, Zhang B, Liu J, Zhang P, Li Z, Luan Y (2015) Green fabricated reduced graphene oxide: evaluation of its application as nano-carrier for pH-sensitive drug delivery. Int J Pharm 496:984–992
Rao Z, Ge H, Liu L, Zhu C, Min L, Liu M, Fan L, Li D (2018) Carboxymethyl cellulose modified graphene oxide as pH-sensitive drug delivery system. Int J Biol Macromol 107:1184–1192
Rasoulzadeh M, Namazi H (2017) Carboxymethyl cellulose/graphene oxide bio-nanocomposite hydrogel beads as anticancer drug carrier agent. Carbohydr Polym 168:320–326
Nivethaa EAK, Dhanavel S, Narayanan V, Stephen A (2016) Fabrication of chitosan/MWCNT nanocomposite as a carrier for 5-fluorouracil and a study of the cytotoxicity of 5-fluorouracil encapsulated nanocomposite towards MCF-7. Polym Bull 73:3221–3236
Yang H, Bremner DH, Tao L, Li H, Hu J, Zhu L (2016) Carboxymethyl chitosan-mediated synthesis of hyaluronic acid-targeted graphene oxide for cancer drug delivery. Carbohydr Polym 135:72–78
Justin R, Chen B (2014) Body temperature reduction of graphene oxide through chitosan functionalisation and its application in drug delivery. Mater Sci Eng C 34:50–53
Dhanavel S, Nivethaa EAK, Narayanan V, Stephen A (2017) In vitro cytotoxicity study of dual drug loaded chitosan/palladium nanocomposite towards HT-29 cancer cells. Mater Sci Eng C 75:1399–1410
Anitha A, Deepa N, Chennazhi KP, Lakshmanan V-K, Jayakumar R (2014) Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment. Biochim Biophys Acta BBA General Subj 1840:2730–2743
Saranya TS, Rajan VK, Biswas R, Jayakumar R, Sathianarayanan S (2018) Synthesis, characterisation and biomedical applications of curcumin conjugated chitosan microspheres. Int J Biol Macromol 110:227–233
Anitha A, Deepagan VG, Divya Rani VV, Menon D, Nair SV, Jayakumar R (2011) Preparation, characterization, in vitro drug release and biological studies of curcumin loaded dextran sulphate–chitosan nanoparticles. Carbohydr Polym 84:1158–1164
Hatamie S, Akhavan O, Sadrnezhaad SK, Ahadian MM, Shirolkar MM, Wang HQ (2015) Curcumin-reduced graphene oxide sheets and their effects on human breast cancer cells. Mater Sci Eng C 55:482–489
Facchi SP, Scariot DB, Bueno PVA, Souza PR, Figueiredo LC, Follmann HDM, Nunes CS, Monteiro JP, Bonafé EG, Nakamura CV, Muniz EC, Martins AF (2016) Preparation and cytotoxicity of N-modified chitosan nanoparticles applied in curcumin delivery. Int J Biol Macromol 87:237–245
Zhang J, Li J, Shi Z, Yang Y, Xie X, Lee SM, Wang Y, Leong KW, Chen M (2017) pH-sensitive polymeric nanoparticles for co-delivery of doxorubicin and curcumin to treat cancer via enhanced pro-apoptotic and anti-angiogenic activities. Acta Biomater 58:349–364
Zhao X, Chen Q, Li Y, Tang H, Liu W, Yang X (2015) Doxorubicin and curcumin co-delivery by lipid nanoparticles for enhanced treatment of diethylnitrosamine-induced hepatocellular carcinoma in mice. Eur J Pharm Biopharm 93:27–36
Brito EL, Gomes DN, Plá Cid CC, de Araújo JCR, Bohn F, Streck L, Fonseca JLC (2019) Superparamagnetic magnetite/IPEC particles. Coll Surf A Physicochem Eng Aspects 560:376–383
Revathy TA, Dhanavel S, Sivaranjani T, Narayanan V, Maiyalagan T, Stephen A (2018) Highly active graphene-supported palladium-nickel alloy nanoparticles for catalytic reduction of 4-nitrophenol. Appl Surf Sci 449:764–771
Nivethaa EAK, Narayanan V, Stephen A (2015) Synthesis and spectral characterization of silver embedded chitosan matrix nanocomposite for the selective colorimetric sensing of toxic mercury. Spectrochim Acta Part A Mol Biomol Spectrosc 143:242–250
Sangamithirai D, Narayanan V, Muthuraaman B, Stephen A (2015) Investigations on the performance of poly(o-anisidine)/graphene nanocomposites for the electrochemical detection of NADH. Mater Sci Eng C 55:579–591
Bhoomika J, Kiran C, Vrinda T, Mhir J (2018) Synthesis and characterization of novel bio-material: nano composites of hydroxyapatite and curcumin. Int J Appl Ceram Technol 15:148–160
Dhanavel S, Nivethaa EAK, Dhanapal K, Gupta VK, Narayanan V, Stephen A (2016) [small alpha]-MoO3/polyaniline composite for effective scavenging of rhodamine B, congo red and textile dye effluent. RSC Adv 6:28871–28886
Safari M, Ghiaci M, Jafari-Asl M, Ensafi AA (2015) Nanohybrid organic–inorganic chitosan/dopamine/TiO2 composites with controlled drug-delivery properties. Appl Surf Sci 342:26–33
Kumar MP, Kesavan T, Kalita G, Ragupathy P, Narayanan TN, Pattanayak DK (2014) On the large capacitance of nitrogen doped graphene derived by a facile route. RSC Adv 4:38689–38697
Zhang Y, Ma H-L, Zhang Q, Peng J, Li J, Zhai M, Yu Z-Z (2012) Facile synthesis of well-dispersed graphene by [gamma]-ray induced reduction of graphene oxide. J Mater Chem 22:13064–13069
Nivethaa EAK, Dhanavel S, Narayanan V, Stephen A (2017) Chitosan stabilized Ag–Au nanoalloy for colorimetric sensing and 5-fluorouracil delivery. Int J Biol Macromol 95:862–872
Sun L, Chen Y, Zhou Y, Guo D, Fan Y, Guo F, Zheng Y, Chen W (2017) Preparation of 5-fluorouracil-loaded chitosan nanoparticles and study of the sustained release in vitro and in vivo. Asian J Pharm Sci 12:418–423
Mirnejad R, Mofazzal Jahromi MA, Al-Musawi S, Pirestani M, Fasihi Ramandi M, Ahmadi K, Rajayi H, Mohammad Hassan Z, Kamali M (2014) Curcumin-loaded chitosan tripolyphosphate nanoparticles as a safe, natural and effective antibiotic inhibits the infection of Staphylococcus aureus and Pseudomonas aeruginosa in vivo. Iran J Biotechnol 12:1–8
Xiao B, Si X, Han MK, Viennois E, Zhang M, Merlin D (2015) Co-delivery of camptothecin and curcumin by cationic polymeric nanoparticles for synergistic colon cancer combination chemotherapy. J Mater Chem B 3:7724–7733
Khoee S, Saadatinia A, Bafkary R (2017) Ultrasound-assisted synthesis of pH-responsive nanovector based on PEG/chitosan coated magnetite nanoparticles for 5-FU delivery. Ultrason Sonochem 39:144–152
Li R, Deng L, Cai Z, Zhang S, Wang K, Li L, Ding S, Zhou C (2017) Liposomes coated with thiolated chitosan as drug carriers of curcumin. Mater Sci Eng C 80:156–164
Nivethaa EAK, Dhanavel S, Rebekah A, Narayanan V, Stephen A (2016) A comparative study of 5-Fluorouracil release from chitosan/silver and chitosan/silver/MWCNT nanocomposites and their cytotoxicity towards MCF-7. Mater Sci Eng C 66:244–250
Acknowledgements
Author SD thanks UGC-UPE-Phase II for its financial aid as fellowship to carry out this research successfully. The authors would like to acknowledge Dr. J. Senthilselvan, Asst. Professor, Department of Nuclear Physics, University of Madras, for his support and helpful discussions.
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Dhanavel, S., Revathy, T.A., Sivaranjani, T. et al. 5-Fluorouracil and curcumin co-encapsulated chitosan/reduced graphene oxide nanocomposites against human colon cancer cell lines. Polym. Bull. 77, 213–233 (2020). https://doi.org/10.1007/s00289-019-02734-x
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DOI: https://doi.org/10.1007/s00289-019-02734-x