Abstract
In the present study design, the PEGylated nanoceria decorated reduced graphene nanocomposite (RGO-CeNPs-PEG) was successfully prepared by eco-friendly non-toxic green synthesis following syn-graphenization method, and evaluated as an efficient and reliable pH-sensitive nano-carrier. During green synthesis, aqueous leaf extract of Azadirachta indica (neem) was used as a reducing agent and the graphene oxide (GO) was activated by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide for covalent functionalization by methoxy amino polyethylene glycol. The prepared Smart pH stimuli responded nanoplatform was thoroughly characterized by various analytical techniques. The values of average particle size and hydrodynamic diameter of naturally prepared nanoceria may be suitable for biomedical application. Considering drug loading and release studies, it may be concluded that the higher drug loading and more pH-responsive release of DOX from RGO-CeNPs-PEG lead to a promising nanocarrier for the anticancer drug. Furthermore, DOX-loaded RGO-CeNPs-PEG had lesser harmful effect on normal cells than cancer cells as compared with free DOX, while increased cytotoxicity was evidenced on the cancer cell line against the former sample than the covalently conjugated RGO-PEG-DOX. So, the successful distribution and release of the anticancer drug into acidic microenvironment of the cancerous cells would bring about excellent therapeutic efficacy with reduced side effects than pure GO.
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W. Zhang, Z. Guo, D. Huang, Z. Liu, X. Guo, and H. Zhong (2011). Biomaterials 32, 8555–8561. https://doi.org/10.1016/j.biomaterials.2011.07.071.
F. S. Sangsefidi, M. Nejati, J. Verdi, and M. Salavati-Niasari (2017). J. Clean Prod. 156, 741–749. https://doi.org/10.1016/j.jclepro.2017.04.114.
M. V. Arasu, R. Thirumamagal, M. P. Srinivasan, N. A. Al-Dhabi, A. Ayeshamariam, D. Saravana Kumar, N. Punithavelan, and M. Jayachandran (2017). J. Photochem. Photobiol. B: Biology 173, 50–60. http://dx.doi.org/10.1016/j.jphotobiol.2017.05.032.
L. Zhang, Z. Wang, Z. Lu, H. Shen, J. Huang, Q. Zhao, M. Liu, N. He, and Z. Zhang (2013). J. Mater. Chem. B 1, 749–755. https://doi.org/10.1039/C2TB00096B.
S. Stankovich, R. D. Piner, X. Q. Chen, N. Q. Wu, S. T. Nguyen, and R. S. Ruoff (2006). J. Mater. Chem. 16, 155–158. https://doi.org/10.1039/B512799H.
Z. M. Milani, F. Charbgoo, and M. Darroudi (2017). Ceram. Int. 43, 14572–14581. https://doi.org/10.1016/j.ceramint.2017.08.177.
S. Simoes, J. N. Moreira, C. Fonseca, N. Düzgüneş, and M. C. P. de Lima (2004). Adv. Drug Deliv. Rev. 56, 947–965. https://doi.org/10.1016/j.addr.2003.10.038.
A. E. Felber, M.-H. Dufresne, and J.-C. Leroux (2012). Adv. Drug Deliv. Rev. 64, 979–992. https://doi.org/10.1016/j.addr.2011.09.006.
Y.-S. Huang, Y.-J. Lu, and J.-P. Chen (2017). J. Magn. Magn. Mater. 427, 34–40. https://doi.org/10.1016/j.jmmm.2016.10.042.
S. Sangomla, M. A. Saifi, A. Khurana, and C. Godugu (2018). J. Trace Elem. Med. Biol. 47, 53–62. https://doi.org/10.1016/j.jtemb.2018.01.016.
B. Ardeshirzadeh, N. A. Anaraki, M. Irani, L. R. Rad, and S. Shamshiri (2015). Mater. Sci. Eng. C 48, 384–390. https://doi.org/10.1016/j.msec.2014.12.039.
H. Lei, M. Xie, Y. Zhao, F. Zhang, Y. Xu, and J. Xie (2016). Ceram. Int. 42, 17798–17805. https://doi.org/10.1016/j.ceramint.2016.08.108.
H. E. Liying, S. U. Yumin, J. Lanhong, and S. H. I. Shikao (2015). J. Rare Earths 33, 791–799. https://doi.org/10.1016/S1002-0721(14)60486-5.
L. Peng, X. He, P. Zhang, J. Zhang, Y. Li, J. Zhang, Y. Ma, Y. Ding, Z. Wu, Z. Chai, and Z. Zhang (2014). J. Mol. Sci. 15, 6072–6085. https://doi.org/10.3390/ijms15046072.
B. Mandal and A. Mondal (2015). RSC Adv. 5, 43081–43091. https://doi.org/10.1039/C5RA03758A.
S. Zhang, K. Yang, L. Z. Feng, and Z. Liu (2011). Carbon 49, 4040–4049. https://doi.org/10.1016/j.carbon.2011.05.056.
T. Zhou, X. Zhou, and D. Xing (2014). Biomaterials 35, 4185–4194. https://doi.org/10.1016/j.biomaterials.2014.01.044.
D. Dutta, R. Mukherjee, M. Patra, M. Banik, R. Dasgupta, M. Mukherjee, and T. Basu (2016). Colloids Surf. B: Biointerfaces 147, 45–53. https://doi.org/10.1016/j.colsurfb.2016.07.045.
K. Anupriya, E. Vivek, and B. Subramanian (2014). J. Alloys Compd. 590, 406–410. https://doi.org/10.1016/j.jallcom.2013.12.121.
Y.-M. Li, X.-P. Chang, Y.-J. Cheng, S. Chen, F. He, and R.-X. Zhuo (2017). Colloids Surf. B: Biointerfaces 153, 220–228. https://doi.org/10.1016/j.colsurfb.2017.02.022.
A. R. K. Sasikala, R. G. Thomas, A. R. Unnithan, B. Saravanakumar, Y. Y. Jeong, C. H. Park, and C. S. Kim (2016). Sci. Rep. 6, 20543. https://doi.org/10.1038/srep20543.
H. El-Hamshary, M. H. El-Newehy, M. M. Abdulhameed, A. El-Faham, and A. S. Elsherbiny (2019). Mater. Chem. Phys. 225, 122–132. https://doi.org/10.1016/j.matchemphys.2018.12.054.
S. Gurunathan, J. W. Han, V. Eppakayala, and J.-H. Kim (2013). Colloids Surf. B: Biointerfaces 102, 772–777. https://doi.org/10.1016/j.colsurfb.2012.09.011.
T. Pirmohamed, J. M. Dowding, S. Singh, B. Wasserman, E. Heckert, A. S. Karakoti, J. E. King, S. Seal, and W. T. Self (2010). Chem. Commun. 46, 2736–2738. https://doi.org/10.1039/B922024K.
G. Cheng, W. Guo, L. Han, E. Chen, L. Kong, L. Wang, W. Ai, N. Song, H. Li, and H. Chen (2013). Toxicol. In Vitro 27, 1082–1088. https://doi.org/10.1016/j.tiv.2013.02.005.
A. S. Karakoti, S. Singh, A. Kumar, M. Malinska, S. V. Kuchibhatla, K. Wozniak, W. T. Self, and S. Seal (2009). J. Am. Chem. Soc. 131, 14144–14145. https://doi.org/10.1021/ja9051087.
Y. Xu, Z. Liu, X. Zhang, Y. Wang, J. Tian, Y. Huang, Y. Ma, X. Zhang, and Y. Chen, Adv. Mater. 21, 1275-1279. https://doi.org/10.1002/adma.200801617.
J. Shen, M. Shi, B. Yan, H. Ma, N. Li, Y. Hu, and M. Ye (2010). Colloids Surf. B: Biointerfaces 82, 434–438. https://doi.org/10.1016/j.colsurfb.2010.07.035.
J. Calvache-Muñoz, F. A. Prado, and J. E. Rodríguez-Páez (2017). Colloids Surf. A 529, 146–159. https://doi.org/10.1016/j.colsurfa.2017.05.059.
S. A. Khan and A. Ahmad (2013). Mater. Res. Bull. 48, 4134–4138. https://doi.org/10.1016/j.materresbull.2013.06.038.
S. Chaudhary, P. Sharma, R. Kumar, and S. K. Mehta (2015). Ceram. Int. 41, 10995–11003. https://doi.org/10.1016/j.ceramint.2015.05.044.
D. K. Subbiah, A. J. Kulandaisamy, R. B. George, P. Shankar, G. K. Mani, K. J. Babu, and J. B. B. Rayappan (2018). J. Alloys Compd. 753, 771–780. https://doi.org/10.1016/j.jallcom.2018.04.248.
X. Yang, Y. Ouyang, F. Wub, Y. Hub, Y. Jib, and Z. Wu (2017). Sens. Actuators B 238, 40–47. https://doi.org/10.1016/j.snb.2016.07.016.
Z. Ji, X. Shen, J. Yang, G. Zhu, and K. Chen (2014). Appl. Catal. B Environ. 144, 454–461. https://doi.org/10.1016/j.apcatb.2013.07.052.
Y. H. Park, S. Y. Park, and I. In (2015). J. Ind. Eng. Chem. 30, 190–196. https://doi.org/10.1016/j.jiec.2015.05.021.
M. Siriviriyanun, T. Popova, L. V. Imae, C. Y. Kiew, W. F. Looi, H. B. Lee Wong, and L. Y. Chung (2015). Chem. Eng. J. 281, 771–781. https://doi.org/10.1016/j.cej.2015.07.024.
M. J. Kishor Kumar and J. T. Kalathi (2018). J. Alloys Compd. 748, 348–354. https://doi.org/10.1016/j.jallcom.2018.03.096.
H. Li, C. Li, C. Jiao, and S. Wang (2015). Ceram. Int. 41, 10170–10176. https://doi.org/10.1016/j.ceramint.2015.04.118.
K. Krishnamoorthy, M. Veerapandian, K. Yun, and S.-J. Kim (2013). Carbon 53, 38–49. https://doi.org/10.1016/j.carbon.2012.10.013.
J. Li, G. Wang, H. Zhu, M. Zhang, X. Zheng, Z. Di, X. Liu, and X. Wang (2014). Sci. Rep. 4, 4359. https://doi.org/10.1038/srep04359.
S. Thakur and P. Patil (2014). Sens. Actuators B 194, 260–268. https://doi.org/10.1016/j.snb.2013.12.067.
R. Singh and S. Singh (2015). Colloids Surfaces B Biointerfaces 132, 78–84. https://doi.org/10.1016/j.colsurfb.2015.05.005.
H. J. Byeon, Q. le Thao, S. Lee, S. Y. Min, E. S. Lee, B. S. Shin, H. G. Choi, and Y. S. Youn (2016). J. Control. Release 225, 301–313. https://doi.org/10.1016/j.jconrel.2016.01.046.
R. Gessner, A. Waicz, B.-R. Lieske, K. Mäder Paulke, and R. Müller (2000). Int. J. Pharm. 196, 245–249. https://doi.org/10.1016/S0378-5173(99)00432-9.
S. Honary and F. Z. Mazandaran (2013). Trop. J. Pharm. Res. 12, 265–273. https://doi.org/10.4314/tjpr.v12i2.20.
P. R. Sarika and N. R. James (2016). Carbohydr. Polym. 148, 354–361. https://doi.org/10.1016/j.carbpol.2016.04.073.
Y. Lv, L. Tao, S. W. A. Bligh, H. Yang, Q. Pan, and L. Zhu (2016). Mater. Sci. Eng. C 59, 652–660. https://doi.org/10.1016/j.msec.2015.10.065.
S. Patra, S. Mukherjee, A. K. Barui, A. Ganguly, B. Sreedhar, and C. R. Patra (2015). Mater. Sci. Eng. C 53, 298–309. https://doi.org/10.1016/j.msec.2015.04.048.
C. Elvira, A. Gallardo, J. S. Roman, and A. Cifuentes (2005). Molecules 10, 114–125. https://doi.org/10.3390/10010114.
X. Wang, C. Li, N. Fan, J. Li, Z. He, and J. Sun (2017). Mater. Sci. Eng. C 78, 370–375. https://doi.org/10.1016/j.msec.2017.04.060.
S. Bayda, M. Hadla, S. Palazzolo, V. Kumar, I. Caligiuri, E. Ambrosi, E. Pontoglio, M. Agostini, T. Tuccinardi, A. Benedetti, P. Riello, V. Canzonieri, G. Corona, G. Toffoli, and F. Rizzolio (2017). J. Control. Release 248, 144–152. https://doi.org/10.1016/j.jconrel.2017.01.022.
X. Zhang, L. Meng, Q. Lu, Z. Fei, and P. J. Dyson (2009). Biomaterials 30, 6041–6047. https://doi.org/10.1016/j.biomaterials.2009.07.025.
Y. Fu and W. J. Kao (2010). Expert Opin. Drug Deliv. 7, 429–444. https://doi.org/10.1517/17425241003602259.
K. Yang, J. Wan, S. Zhang, Y. Zhang, S.-T. Lee, and Z. Liu (2011). ACS Nano 5, 516–522. https://doi.org/10.1021/nn1024303.
J. M. Perez, A. Asati, S. Nath, and C. Kaittanis (2008). Small 4, 552–556. https://doi.org/10.1002/smll.200700824.
J. Chen, H. Liu, C. Zhao, G. Qin, G. Xi, T. Li, X. Wang, and T. Chen (2014). Biomaterials 35, 4986–4995. https://doi.org/10.1016/j.biomaterials.2014.02.032.
L. P. Franchi, B. B. Manshian, T. A. J. de Souza, S. J. Soenen, E. Y. Matsubara, J. M. Rosolen, and C. S. Takahashi (2015). Toxicol. In Vitro 29, 1319–1331. https://doi.org/10.1016/j.tiv.2015.05.010.
M. S. Wason, J. Colon, S. Das, S. Seal, J. Turkson, J. Zhao, and C. H. Baker (2013). Nanomed. Nanotechnol. Biol. Med. 9, 558–569. https://doi.org/10.1016/j.nano.2012.10.010.
M. Darroudi, M. Hakimi, M. Sarani, R. K. Oskuee, A. K. Zak, and L. Gholami (2013). Ceram. Int. 39, 6917–6921. https://doi.org/10.1016/j.ceramint.2013.02.026.
J. Colon, N. Hsieh, A. Ferguson, P. Kupelian, S. Seal, D. W. Jenkins, and C. H. Baker (2010). Nanomed. Nanotechnol. Biol. Med. 6, 698–705. https://doi.org/10.1016/j.nano.2010.01.010.
M. S. Lord, M. S. Jung, W. Y. Teoh, C. Gunawan, J. A. Vassie, R. Amal, and J. M. Whitelock (2012). Biomaterials 33, 7915–7924. https://doi.org/10.1016/j.biomaterials.2012.07.024.
L. D. Marzi, A. Monaco, J. D. Lapuente, D. Ramos, M. Borras, M. D. Gioacchino, S. Santucci, and A. Poma (2013). Int. J. Mol. Sci. 14, 3065–3077. https://doi.org/10.3390/ijms14023065.
M. Pešić, A. Podolski-Renić, S. Stojković, B. Matović, D. Zmejkoski, V. Kojić, G. Bogdanović, A. Pavićević, M. Mojović, A. Savić, I. Milenković, A. Kalauzi, and K. Radotić (2015). Chem. Biol. Interact. 232, (85–93), 2015. https://doi.org/10.1016/j.cbi.2015.03.0130009-2797/.
F. Abbas, T. Jan, J. Iqbal, and M. S. H. Naqvi (2015). Curr. Appl. Phys. 15, 1428–1434. https://doi.org/10.1016/j.cap.2015.08.007.
R. Justin, K. Tao, S. Román, D. Chen, Y. Xu, X. Geng, I. M. Ross, R. T. Grant, A. Pearson, G. Zhou, S. M. Neil, K. Sun, and B. Chen (2016). Carbon 97, 54–70. https://doi.org/10.1016/j.carbon.2015.06.070.
P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref (2010). Nat. Mater. 9, 172–178. https://doi.org/10.1038/nmat2608.
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Palai, P.K., Mondal, A., Chakraborti, C.K. et al. Doxorubicin Loaded Green Synthesized Nanoceria Decorated Functionalized Graphene Nanocomposite for Cancer-Specific Drug Release. J Clust Sci 30, 1565–1582 (2019). https://doi.org/10.1007/s10876-019-01599-4
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DOI: https://doi.org/10.1007/s10876-019-01599-4