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176 Carbon-Based Nanocarriers for Drug Delivery
DOX-loaded ZIF-8/GQD nanoparticles, raising the temperature further. More crucially, the outcomes demonstrated that the combination of chemo- and photothermal
treatment with DOX-ZIF-8/GQD nanoparticles had a notable interdependent effect
using breast cancer 4T1 cells as a model cellular system. Relative to chemotherapy
and photothermal treatment separately, the combined impact has a better efcacy in
eradicating cancer cells. As exible nanocarriers for combinatorial cancer treatment,
ZIF-8/GQD nanoparticles are therefore expected to show promise [78].
The GQDs have displayedinherent photothermal and photodynamic characteristics and applicability toward drug delivery. However, further investigations are
required in the area of combined therapies to improve the loading efciency and
pH-responsive release behavior of chemotherapeutic agents.
6.6 SUMMARY
The present chapter summarizes the recent developments in the synthesis of GQDs
via top-down and bottom-up approaches with various functionalization strategies
to improve their surface and physicochemical characteristics. It was observed that
the diversity in the size, structure, and functionalized form of GQDs results in a
number of modications to their physical, biological,chemical, optical, and electrical characteristics. Both the top-down and bottom-up approaches for the synthesis of
GQDs have affected the aqueous stability of the GQDs by reducing the oxygenated
functional entities. In addition, some of these methods, such as microwave, ultrasound, and hydrothermal methods, are considered highly energy intensive, which
enhances their operating cost and limits their large-scale application. Meanwhile,
the optimization of process parameters and the use of green synthesis methods may
overcome these shortcomings. Also, specically, the bottom-up approaches suffer
from low quantum yield, which is a major drawback of these methods.
Herein, the recent developments related to the application of GQDs in the eld
of drug delivery, gene therapy, and phototherapy have also been discussed. It was
observed that GQDs, with their small size, low toxicity, and aqueous stability, have
provided signicant advantages for drug delivery. However, for their large-scale
manufacturing and commercial usage, these formulations’ toxicity still has to be
improved. The biocompatibility of GQD-based nanoformulations can be improved by
using green manufacturing techniques and natural chemotherapeutic agents, which
need to be investigated for their application. For the further application of GQDs in
the biomedical eld, thefunctionalization approaches must be adapted using various
biopolymers to improve theirdispersion stability.It is not necessary to use a lot of
GQDs for drug delivery applications, but their regulated size and purity must be considered. Overall, GQDs have displayed signicant potential for drug delivery-related
applications, specically in anticancer therapeutics.
REFERENCES
[1] J. Douda, C.R. González Vargas, E.V. Basiuk, A.I. Díaz Cano, J.A. Fuentes García, X.A.
Hernández Contreras, Optical properties of amine-functionalized graphene oxide, Appl.
Nanosci. 9 (2019) 567–578. doi:10.1007/s13204-019-00956-z.

177Graphene Quantum Dots for Drug Delivery
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
[2] M. Dahiya, S.A. Bansal, Graphene-reinforced nanocomposites: Synthesis, microme-
chanics models, analysis and applications—a review, Proc. Inst. Mech. Eng. Part C J.
Mech. Eng. Sci. 236 (2022) 9218–9240. doi:10.1177/09544062221091773.
[3] C. Lee, X. Wei, J.W. Kysar, J. Hone, Measurement of the elastic properties and intrinsic
strength of monolayer graphene, Sci. 321 (2008) 385–388. doi:10.1126/science.1157996.
[4] C. Fang, J. Zhang, X. Chen, G.J. Weng, Calculating the electrical conductivity of graphene
nanoplatelet polymer composites by a Monte Carlo method, Nanomat. 10 (2020) 1129.
doi:10.3390/nano10061129.
[5] M.S. Iyer, W. Fu-Ming, I. Rajangam, Electrochemical detection of CA125 using thionine
and gold nanoparticles supported on heteroatom-doped graphene nanocomposites, Appl.
Nanosci. 11 (2021) 2167–2180. doi:10.1007/s13204-021-01966-6.
[6] E.-C. Cho, J.-H. Huang, C.-P. Li, C.-W. Chang-Jian, K.-C. Lee, Y.-S. Hsiao, J.-H. Huang,
Graphene-based thermoplastic composites and their application for LED thermal management, Carbon N. Y. 102 (2016) 66–73. doi:10.1016/j.carbon.2016.01.097.
[7] A.A. Balandin, S. Ghosh, W. Bao, I. Calizo, D. Teweldebrhan, F. Miao, C.N. Lau,
Superior thermal conductivity of single-layer graphene, Nano Lett. 8 (2008) 902–907.
doi:10.1021/nl0731872.
[8] A. Kalluri, D. Debnath, B. Dharmadhikari, P. Patra, Graphene quantum dots: Synthe-
sis and applications, in: E. Kumar (Ed.), Enzyme Nanoarchitectures Enzyme Armored
with Graphene, Academic Press, New York (2018): pp.
335–354. doi:10.1016/
bs.mie.2018.07.002.
[9] N.S. Samanta, S. Banerjee, P. Mondal, Anweshan, U. Bora, M.K. Purkait, Preparation
and characterization of zeolite from waste Linz-Donawitz (LD) process slag of steel
industry for removal of Fe3+ from drinking water, Adv. Powder Technol. 32 (2021)
3372–3387. doi:10.1016/j.apt.2021.07.023.
[10] M.C. Biswas, M.T. Islam, P.K. Nandy, M.M. Hossain, Graphene quantum dots (GQDs)
for bioimaging and drug delivery applications: A
review, ACS Mater. Lett. 3 (2021) 889–
911. doi:10.1021/acsmaterialslett.0c00550.
[11] C. Zhao, X. Song, Y. Liu, Y. Fu, L. Ye, N. Wang, F. Wang, L. Li, M. Mohammadniaei,
M. Zhang, Q. Zhang, J. Liu, Synthesis of graphene quantum dots and their applications
in drug delivery, J. Nanobiotechnol. 18 (2020) 142. doi:10.1186/s12951-020-00698-z.
[12] M. Bacon, S.J. Bradley, T. Nann, Graphene quantum dots, Part. Part. Syst. Charact. 31
(2014) 415–428. doi:10.1002/ppsc.201300252.
[13] Z. Farka, T. Juřík, D. Kovář, L. Trnková, P. Skládal, Nanoparticle-based immunochem-
ical biosensors and assays: Recent advances and challenges, Chem. Rev. 117 (2017)
9973–10042. doi:10.1021/acs.chemrev.7b00037.
[14] J.K. Kim, M.J. Park, S.J. Kim, D.H. Wang, S.P. Cho, S. Bae, J.H. Park, B.H. Hong,
Balancing light absorptivity and carrier conductivity of graphene quantum dots for highefciency bulk heterojunction solar cells, ACS Nano. 7 (2013) 7207–7212. doi:10.1021/
nn402606v.
[15] H. Wang, P. Agarwal, S. Zhao, J. Yu, X. Lu, X. He, A biomimetic hybrid nanoplatform
for encapsulation and precisely controlled delivery of theranostic agents, Nat. Commun.
6 (2015). doi:10.1038/ncomms10081.
[16] F. Chen, W. Gao, X. Qiu, H. Zhang, L. Liu, P. Liao, W. Fu, Y. Luo, Graphene quantum
dots in biomedical applications: Recent advances and future challenges, Front. Lab. Med.
1 (2017) 192–199. doi:10.1016/j.m.2017.12.006.
[17] X. Wang, X. Sun, J. Lao, H. He, T. Cheng, M. Wang, S. Wang, F. Huang, Multifunctional
graphene quantum dots for simultaneous targeted cellular imaging and drug delivery,
Colloids Surf. B Biointerfaces. 122 (2014) 638–644. doi:10.1016/j.colsurfb.2014.07.043.
[18] G. Perini, V. Palmieri, G. Ciasca, M. De Spirito, M. Papi, Unravelling the potential of
graphene quantum dots in biomedicine and neuroscience, Int. J. Mol. Sci. 21 (2020)
3712. doi:10.3390/ijms21103712.

178 Carbon-Based Nanocarriers for Drug Delivery
[19] Z. Zeng, S. Chen, T.T.Y. Tan, F.-X. Xiao, Graphene quantum dots (GQDs) and its deriva-
tives for multifarious photocatalysis and photoelectrocatalysis, Catal. Today. 315 (2018)
171–183. doi:10.1016/j.cattod.2018.01.005.
[20] Y. Wang, J. Li, X. Li, J. Shi, Z. Jiang, C.Y. Zhang, Graphene-based nanomaterials for
cancer therapy and anti-infections, Bioact. Mater. 14 (2022) 335–349. doi:10.1016/j.
bioactmat.2022.01.045.
[21] P. Kumar, C. Dhand, N. Dwivedi, S. Singh, R. Khan, S. Verma, A. Singh, M.K. Gupta,
S. Kumar, R. Kumar, A.K. Srivastava, Graphene quantum dots: A contemporary perspective on scope, opportunities, and sustainability, Renew. Sustain. Energy Rev. 157 (2022)
111993. doi:10.1016/j.rser.2021.111993.
[22] S. Kumbhar, M. De, Carbon quantum dots modied Bi2WO6 nanosheets for photo-
oxidation of glycerol to value-added product, Mater. Today Proc. (2022). doi:10.1016/j.
matpr.2022.11.230.
[23] C. Wang, C. Wu, X. Zhou, T. Han, X. Xin, J. Wu, J. Zhang, S. Guo, Enhancing cell
nucleus accumulation and DNA cleavage activity of anti-cancer drug via graphene quantum dots, Sci. Rep. 3 (2013) 2852. doi:10.1038/srep02852.
[24] D. Iannazzo, A. Pistone, M. Salamò, S. Galvagno, R. Romeo, S. V. Giofré, C. Branca,
G. Visalli, A. Di Pietro, Graphene quantum dots for cancer targeted drug delivery, Int.
J. Pharm. 518 (2017) 185–192. doi:10.1016/j.ijpharm.2016.12.060.
[25] S. Zhu, Y. Song, J. Wang, H. Wan, Y. Zhang, Y. Ning, B. Yang, Photoluminescence mech-
anism in graphene quantum dots: Quantum connement effect and surface/edge state,
Nano Today. 13 (2017) 10–14. doi:10.1016/j.nantod.2016.12.006.
[26] J. Shen, Y. Zhu, X. Yang, C. Li, Graphene quantum dots: Emergent nanolights for bio-
imaging, sensors, catalysis and photovoltaic devices, Chem. Commun. 48 (2012) 3686.
doi:10.1039/c2cc00110a.
[27] A.D. Sontakke, M.K. Purkait, Fabrication of ultrasound-mediated tunable graphene
oxide nanoscrolls, Ultrason. Sonochem. 63 (2020) 104976. doi:10.1016/j.ultsonch.2020.
104976.
[28] A.D. Sontakke, R. Fopase, L.M. Pandey, M.K. Purkait, Development of graphene oxide
nanoscrolls imparted nano-delivery system for the sustained release of gallic acid, Appl.
Nanosci. (2022). doi:10.1007/s13204-022-02582-8.
[29] A.D. Sontakke, M.K. Purkait, A brief review on graphene oxide nanoscrolls: Structure,
Synthesis, characterization and scope of applications, Chem. Eng. J. 420 (2021) 129914.
doi:10.1016/j.cej.2021.129914.
[30] P. Mondal, A. Anweshan, M.K. Purkait, Green synthesis and environmental application
of iron-based nanomaterials and nanocomposite: A review, Chemosphere. 259 (2020)
127509. doi:10.1016/j.chemosphere.2020.127509.
[31] H. Huang, S. Yang, Q. Li, Y. Yang, G. Wang, X. You, B. Mao, H. Wang, Y. Ma, P. He, Z.
Liu, G. Ding, X. Xie, Electrochemical cutting in weak aqueous electrolytes: The strategy
for efcient and controllable preparation of graphene quantum dots, Langmuir. 34 (2018)
250–258. doi:10.1021/acs.langmuir.7b03425.
[32] Y. Li, Y. Zhao, H. Cheng, Y. Hu, G. Shi, L. Dai, L. Qu, Nitrogen-doped graphene quan-
tum dots with oxygen-rich functional groups, J. Am. Chem. Soc. 134 (2012) 15–18.
doi:10.1021/ja206030c.
[33] D. Huang, L. Yin, X. Lu, S. Lin, Z. Niu, J. Niu, Directional electron transfer mechanisms
with graphene quantum dots as the electron donor for photodecomposition of peruorooctane sulfonate, Chem. Eng. J. 323 (2017) 406–414. doi:10.1016/j.cej.2017.04.124.
[34] H. Gao, C. Xue, G. Hu, K. Zhu, Production of graphene quantum dots by ultrasound-as-
sisted exfoliation in supercritical CO2/H2O medium, Ultrason. Sonochem. 37 (2017)
120–127. doi:10.1016/j.ultsonch.2017.01.001.
[35] C. Zhang, Y. Cui, L. Song, X. Liu, Z. Hu, Microwave assisted one-pot synthesis of
graphene quantum dots as highly sensitive uorescent probes for detection of iron ions
and pH value, Talanta. 150 (2016) 54–60. doi:10.1016/j.talanta.2015.12.015.

179Graphene Quantum Dots for Drug Delivery
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
[36] Y. Shin, J. Lee, J. Yang, J. Park, K. Lee, S. Kim, Y. Park, H. Lee, Mass production of
graphene quantum dots by one-pot synthesis directly from graphite in high yield, Small.
10 (2014) 866–870. doi:10.1002/smll.201302286.
[37] Z. Luo, G. Qi, K. Chen, M. Zou, L. Yuwen, X. Zhang, W. Huang, L. Wang, Microwave-
assisted preparation of white uorescent graphene quantum dots as a novel phosphor
for enhanced white-light-emitting diodes, Adv. Funct. Mater. 26 (2016) 2739–2744.
doi:10.1002/adfm.201505044.
[38] J. Shen, Y. Zhu, C. Chen, X. Yang, C. Li, Facile preparation and upconversion lumines-
cence of graphene quantum dots, Chem. Commun. 47 (2011) 2580–2582. doi:10.1039/
C0CC04812G.
[39] J. Peng, W. Gao, B.K. Gupta, Z. Liu, R. Romero-Aburto, L. Ge, L. Song, L.B. Alemany,
X. Zhan, G. Gao, S.A. Vithayathil, B.A. Kaipparettu, A.A. Marti, T. Hayashi, J.-J. Zhu,
P.M. Ajayan, Graphene quantum dots derived from carbon bers, Nano Lett. 12 (2012)
844–849. doi:10.1021/nl2038979.
[40] Q. Lu, C. Wu, D. Liu, H. Wang, W. Su, H. Li, Y. Zhang, S. Yao, A facile and simple
method for synthesis of graphene oxide quantum dots from black carbon, Green Chem.
19 (2017) 900–904. doi:10.1039/C6GC03092K.
[41] R. Tian, S. Zhong, J. Wu, W. Jiang, Y. Shen, W. Jiang, T. Wang, Solvothermal method
to prepare graphene quantum dots by hydrogen peroxide, Opt. Mater. (Amst). 60 (2016)
204–208. doi:10.1016/j.optmat.2016.07.032.
[42] J.-H. Zhang, T. Sun, A. Niu, Y.-M. Tang, S. Deng, W. Luo, Q. Xu, D. Wei, D.-S. Pei, Per-
turbation effect of reduced graphene oxide quantum dots (rGOQDs) on aryl hydrocarbon
receptor (AhR) pathway in zebrash, Biomaterials. 133 (2017) 49–59. doi:10.1016/j.
biomaterials.2017.04.026.
[43] Z. Wang, J. Yu, X. Zhang, N. Li, B. Liu, Y. Li, Y. Wang, W. Wang, Y. Li, L. Zhang, S. Dis-
sanayake, S.L. Suib, L. Sun, Large-scale and controllable synthesis of graphene quantum
dots from rice husk biomass: A
comprehensive utilization strategy, ACS Appl. Mater.
Interfaces. 8 (2016) 1434–1439. doi:10.1021/acsami.5b10660.
[44] D. Liu, X. Chen, Y. Hu, T. Sun, Z. Song, Y. Zheng, Y. Cao, Z. Cai, M. Cao, L. Peng, Y. Huang,
L. Du, W. Yang, G. Chen, D. Wei, A.T.S. Wee, D. Wei, Raman enhancement on ultraclean graphene quantum dots produced by quasi-equilibrium
plasma-enhanced chemical
vapor deposition, Nat. Commun. 9 (2018) 193. doi:10.1038/s41467-017-02627-5.
[45] J. Lee, K. Kim, W.I. Park, B.-H. Kim, J.H. Park, T.-H. Kim, S. Bong, C.-H. Kim, G.
Chae, M. Jun, Y. Hwang, Y.S. Jung, S. Jeon, Uniform graphene quantum dots patterned
from self-assembled silica nanodots, Nano Lett. 12 (2012) 6078–6083. doi:10.1021/
nl302520m.
[46] M.J. Deka, D. Chowdhury, CVD assisted hydrophobic graphene quantum dots: Flu-
orescence sensor for aromatic amino acids, ChemistrySelect. 2 (2017) 1999–2005.
doi:10.1002/slct.201601737.
[47] S. Kumar, S.T. Aziz, O. Girshevitz, G.D. Nessim, One-step synthesis of N-doped
graphene quantum dots from chitosan as a sole precursor using chemical vapor deposition, J. Phys. Chem. C. 122 (2018) 2343–2349. doi:10.1021/acs.jpcc.7b05494.
[48] H.M. Kashani, T. Madrakian, A. Afkhami, F. Mahjoubi, M.A. Moosavi, Bottom-up
and green-synthesis route of amino functionalized graphene quantum dot as a novel
biocompatible and label-free uorescence probe for in vitro cellular imaging of
human ACHN cell lines, Mater. Sci. Eng. B. 251 (2019) 114452. doi:10.1016/j.mseb.
2019.114452.
[49] A. Bayat, E. Saievar-Iranizad, Synthesis of green-photoluminescent single layer graphene
quantum dots: Determination of HOMO and LUMO energy states, J. Lumin. 192 (2017)
180–183. doi:10.1016/j.jlumin.2017.06.055.
[50] X. Wu, F. Tian, W. Wang, J. Chen, M. Wu, J.X. Zhao, Fabrication of highly uorescent
graphene quantum dots using l-glutamic acid for in vitro/in vivo imaging and sensing, J.
Mater. Chem. C. 1 (2013) 4676. doi:10.1039/c3tc30820k.

180 Carbon-Based Nanocarriers for Drug Delivery
[51] Y. Dong, J. Shao, C. Chen, H. Li, R. Wang, Y. Chi, X. Lin, G. Chen, Blue luminescent
graphene quantum dots and graphene oxide prepared by tuning the carbonization degree
of citric acid, Carbon N. Y. 50 (2012) 4738–4743. doi:10.1016/j.carbon.2012.06.002.
[52] L. Wang, W. Li, B. Wu, Z. Li, D. Pan, M. Wu, Room-temperature synthesis of graphene
quantum dots via electron-beam irradiation and their application in cell imaging, Chem.
Eng. J. 309 (2017) 374–380. doi:10.1016/j.cej.2016.10.022.
[53] R. Rabeya, S. Mahalingam, K.S. Lau, A. Manap, M. Satgunam, C.H. Chia, M. Akhtaru-
zzaman, Hydrothermal functionalization of graphene quantum dots extracted from cellulose, Chem. Phys. Lett. 795 (2022) 139520. doi:10.1016/j.cplett.2022.139520.
[54] S. Kadian, S.K. Sethi, G. Manik, Recent advancements in synthesis and property control
of graphene quantum dots for biomedical and optoelectronic applications, Mater. Chem.
Front. 5 (2021) 627–658. doi:10.1039/D0QM00550A.
[55] Z. Qian, J. Ma, X. Shan, L. Shao, J. Zhou, J. Chen, H. Feng, Surface functionalization of
graphene quantum dots with small organic molecules from photoluminescence modulation to bioimaging applications: An experimental and theoretical investigation, RSC Adv.
3 (2013) 14571. doi:10.1039/c3ra42066c.
[56] S.H. Jin, D.H. Kim, G.H. Jun, S.H. Hong, S. Jeon, Tuning the photoluminescence of
graphene quantum dots through the charge transfer effect of functional groups, ACS
Nano. 7 (2013) 1239–1245. doi:10.1021/nn304675g.
[57] X. Yuan, Z. Liu, Z. Guo, Y. Ji, M. Jin, X. Wang, Cellular distribution and cytotoxicity of
graphene quantum dots with different functional groups, Nanoscale Res. Lett. 9 (2014)
108. doi:10.1186/1556-276X-9-108.
[58] Z.M. Markovic, B.Z. Ristic, K.M. Arsikin, D.G. Klisic, L.M. Harhaji-Trajkovic, B.M.
Todorovic-Markovic, D.P. Kepic, T.K. Kravic-Stevovic, S.P. Jovanovic, M.M. Milenkovic, D.D. Milivojevic, V.Z. Bumbasirevic, M.D. Dramicanin, V.S. Trajkovic, Graphene
quantum dots as autophagy-inducing photodynamic agents, Biomaterials. 33 (2012)
7084–7092. doi:10.1016/j.biomaterials.2012.06.060.
[59] C. Luo, Y. Li, L. Guo, F. Zhang, H. Liu, J. Zhang, J. Zheng, J. Zhang, S. Guo, Graphene
quantum dots downregulate multiple multidrug-resistant genes via interacting with their
C-rich promoters, Adv. Healthc. Mater. 6 (2017) 1700328. doi:10.1002/adhm.201700328.
[60] S. Tiwari, A.D. Sontakke, K. Baruah, M.K. Purkait, Development of graphene oxide-
based nano-delivery system for natural chemotherapeutic agent (Caffeic Acid), Mater.
Today Proc. (2022). doi:10.1016/j.matpr.2022.11.373.
[61] A.A. Nahain, J.-E. Lee, I. In, H. Lee, K.D. Lee, J.H. Jeong, S.Y. Park, Target delivery and
cell imaging using hyaluronic acid-functionalized graphene quantum dots, Mol. Pharm.
10 (2013) 3736–3744. doi:10.1021/mp400219u.
[62] F. Nasrollahi, B. Sana, D. Paramelle, S. Ahadian, A. Khademhosseini, S. Lim, Incorpora-
tion of graphene quantum dots, iron, and doxorubicin in/on ferritin nanocages for bimodal
imaging and drug delivery, Adv. Ther. 3 (2020) 1900183. doi:10.1002/adtp.201900183.
[63] S. Javanbakht, H. Namazi, Doxorubicin loaded carboxymethyl cellulose/graphene quan-
tum dot nanocomposite hydrogel lms as a potential anticancer drug delivery system,
Mater. Sci. Eng. C. 87 (2018) 50–59. doi:10.1016/j.msec.2018.02.010.
[64] O. Lv, Y. Tao, Y. Qin, C. Chen, Y. Pan, L. Deng, L. Liu, Y. Kong, Highly uorescent
and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in
vivo imaging and pH-sensitive drug carrier, Mater. Sci. Eng. C. 67 (2016) 478–485.
doi:10.1016/j.msec.2016.05.031.
[65] S.M. Ghafary, M. Nikkhah, S. Hatamie, S. Hosseinkhani, Simultaneous gene deliv-
ery and tracking through preparation of photo-luminescent nanoparticles based on
graphene quantum dots and chimeric peptides, Sci. Rep. 7 (2017) 1–14. doi:10.1038/
s41598-017-09890-y.

181Graphene Quantum Dots for Drug Delivery
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
[66] S. Xiao, D. Zhou, P. Luan, B. Gu, L. Feng, S. Fan, W. Liao, W. Fang, L. Yang, E. Tao,
R. Guo, J. Liu, Graphene quantum dots conjugated neuroprotective peptide improve
learning and memory capability, Biomaterials. 106 (2016) 98–110. doi:10.1016/j.
biomaterials.2016.08.021.
[67] M. Ahn, J. Song, B.H. Hong, Facile synthesis of N-doped graphene quantum dots as novel
transfection agents for mRNA and pDNA, Nanomaterials. 11 (2021) 2816. doi:10.3390/
nano11112816.
[68] H. Zhu, Y. Fang, Q. Miao, X. Qi, D. Ding, P. Chen, K. Pu, Regulating near-infrared pho-
todynamic properties of semiconducting polymer nanotheranostics for optimized cancer
therapy, ACS Nano. 11 (2017) 8998–9009. doi:10.1021/acsnano.7b03507.
[69] A.D. Sontakke, A. Bhattacharjee, R. Fopase, L.M. Pandey, M.K. Purkait, One-pot, sus-
tainable and room temperature synthesis of graphene oxide-impregnated iron-based
metal-organic framework (GO/MIL-100(Fe)) nanocarriers for anticancer drug delivery
systems, J. Mater. Sci. (2022). doi:10.1007/s10853-022-07773-w.
[70] T.A. Tabish, S. Zhang, Graphene quantum dots: Syntheses, properties, and biolog-
ical applications, Compr. Nanosci. Nanotechnol. (2016) 171–192. doi:10.1016/
B978-0-12-803581-8.04133-3.
[71] L. Cheng, X. Wang, F. Gong, T. Liu, Z. Liu, 2D nanomaterials for cancer theranostic
applications, Adv. Mater. 32 (2020) 1902333. doi:10.1002/adma.201902333.
[72] Y. Cao, H. Dong, Z. Yang, X. Zhong, Y. Chen, W. Dai, X. Zhang, Aptamer- conjugated
graphene quantum dots/porphyrin derivative theranostic agent for intracellular
cancer-related microRNA detection and uorescence-guided photothermal/ photodynamic
synergetic therapy, ACS Appl. Mater. Interfaces. 9 (2017) 159–166. doi:10.1021/acsami.
6b13150.
[73] S.Y. Choi, S.H. Baek, S.-J. Chang, Y. Song, R. Raque, K.T. Lee, T.J. Park, Synthesis of
upconversion nanoparticles conjugated with graphene oxide quantum dots and their use
against cancer cell imaging and photodynamic therapy, Biosens. Bioelectron. 93 (2017)
267–273. doi:10.1016/j.bios.2016.08.094.
[74] S.P. Jovanović, Z. Syrgiannis, Z.M. Marković, A. Bonasera, D.P. Kepić, M.D. Budimir,
D.D. Milivojević, V.D. Spasojević, M.D. Dramićanin, V.B. Pavlović, B.M. Todorović
Marković, Modication of structural and luminescence properties of graphene quantum
dots by gamma irradiation and their application in a photodynamic therapy, ACS Appl.
Mater. Interfaces. 7 (2015) 25865–25874. doi:10.1021/acsami.5b08226.
[75] X. Wang, X. Sun, H. He, H. Yang, J. Lao, Y. Song, Y. Xia, H. Xu, X. Zhang, F. Huang,
A two-component active targeting theranostic agent based on graphene quantum dots, J.
Mater. Chem. B. 3 (2015) 3583–3590. doi:10.1039/C5TB00211G.
[76] D. Dong, Z. Wu, J. Wang, G. Fu, Y. Tang, Recent progress in Co
for hydrogen and oxygen electrocatalysis, J. Mater. Chem. A. 7 (2019) 16068–16088.
-based materials
9S8
doi:10.1039/C9TA04972J.
[77] S. Li, S. Zhou, Y. Li, X. Li, J. Zhu, L. Fan, S. Yang, Exceptionally high payload of
the IR780 iodide on folic acid-functionalized graphene quantum dots for targeted photothermal therapy, ACS Appl. Mater. Interfaces. 9 (2017) 22332–22341. doi:10.1021/
acsami.7b07267.
[78] Z. Tian, X. Yao, K. Ma, X. Niu, J. Grothe, Q. Xu, L. Liu, S. Kaskel, Y. Zhu, Metal–organic
framework/graphene quantum dot nanoparticles used for synergistic chemo- and photothermal therapy, ACS Omega. 2 (2017) 1249–1258. doi:10.1021/acsomega.6b00385.

Fullerene-Based Drug
7
Delivery System
7.1 INTRODUCTION TO FULLERENE
Carbon, the most prevalent element in organic molecules, has been shown to occur
in two allotropes: diamond and graphite. Fullerenes, a third kind of carbon, were
discovered in 1985. Smalley, Kroto, and Curl headed a group of scientists that sought
to mimic the environment wherein carbon nucleates in the atmospheres of red giant
stars. In their study, a portion of solid graphite was evaporated into plasma comprising ions and atomsby irradiating it with a laser. Because of the interaction with
the helium atoms, the unbound ions and atoms were cooled. Clusters with varying
quantities of carbon atoms were synthesized because of the collision. When the compounds were analyzed using a mass spectrometer, it was discovered that clusters
between 60 and 70 carbon atoms predominate and that 60 atoms were present in the
majority of clusters [1]. At the outset, the researchers faced difculties in synthesizinga sufcient quantity of fullerenes. They barely managed to prepare around 10–15
g. Nonetheless, it took ve years for Krätschmer and Huffman (1990) [2] and Kroto
etal. (1991) [3] to establish alternative higher-yield sample preparation methodologies for fullerenes. The freshly discovered particle was given the architect Richard
Buckminster Fuller’s title since he designed the dome in 1967, which has the same
form as the carbon clusters [4].
The three researchers who invented fullerenes wereawardedwiththe 1996 Nobel
Prize in Chemistry because fullerenes sparked such fascination and enthusiasm
among scientists and researchers. Eventually, it was discovered that fullerenes naturally occur in both interstellar dust and earthly geological formations, however, only
within the ppm range. Given that there are no substantial changes during the interaction, fullerene is a good candidate for electron transfer processes. As a result, C60
has the ability to effectively slow down charge carrier recombination. Additionally,
fullerene exhibits moderate reactions in the visible spectrum as well as substantial
absorption of U.V. radiation [5]. As a result, it may also function as a suitable sensitizer to emit electrons when paired with a semiconductor photocatalyst after the
irradiation of a visible light source. Fullerene, on the other hand, lacks active areas on
the cages for direct catalytic uses. Signicantly, fullerene cages have a high degree
of hydrophobicity and are inaccessible in polar solvents such as water. Numerous
studies have described adding hydroxyl functional groups to the exterior of fullerene
to integrate it into a polar environment [5].
The present chapter deals with the various structural attributes and physicochemical characteristics of fullerene, along with its signicance and prospects as
a nanocarrier for drug delivery. The methods for synthesizing fullerene, such as
arc discharge, gas-phase, and wet-chemical processes, have been illustrated with
182 DOI: 10.1201/9781003358114-7

183Fullerene-Based Drug Delivery System
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their advancements. Furthermore, the functionalization strategies are highlighted
to enhance the surface characteristics of fullerene. The recent advancements in the
applications of fullerene for nucleic acid delivery, chemotherapeutics, and neurodegenerative diseases have been elucidated in the last section.
7.2 STRUCTURAL FEATURES AND PHYSICOCHEMICAL
PROPERTIES OF FULLERENE
The rst fullerene, C60, was discovered in 1985, but the family of fullerenes also
comprises a large variety of other carbon-based compounds with various symmetries
and atom counts. The most prevalent fullerene, also known as “Buckminsterfullerene,” is made up of 60 carbon atoms organized in 20 hexagons and12 pentagons,
giving it the shape of a hollow sphere (Figure7.1) [6]. The extremely stable and symmetrical structure of C60 garnered a lot of attention. Zero-dimensional fullerenes are
thought to have highly intriguing chemical and physical characteristics for medical
and technological purposes [7].
Fullerenes satisfy Euler’s theorem, which states that exactly 12 pentagons must
be present in a closed construction made of hexagons and pentagons.According to
this criterion, the smallest robust fullerene is C60, with the most rigid form due to
the absence of two adjacent pentagons. The great uniformity of the C60 structure is
a signicant characteristic. The structure is mapped onto itself by 120 symmetrical
functions, including rotation along the axis and reection in a plane. As a result, C60
is the most symmetrical molecule [8]. The fullerene has two different bond lengths:
C5-C5 single bonds in pentagons and C5-C6 double bonds in hexagons, both of which
measure 1.45 ± 0.015 Åand 1.40 ± 0.015 Å, correspondingly [9].
Through sp2 hybridization, each of thecarbon atoms in fullerenejoins three other
nearby atoms. The collection of orbitals is oriented in the xy-plane and is organized
at 120-degree inclinations. Hence, through resonance, such delocalized pi electrons
maintain the spheroid structure [10]. The diameter of a C60 molecule, sometimes
referred to as a Buckyball or Buckminsterfullerene, is around 7 Å. Asolid composed
of loosely linked C60 molecules is synthesized during condensation. Fullerites are
this type of crystal structure. This solid is cubic, weakly bound, electrically insulating, and has a lattice constant of 14.71. It appears as a yellow powder that, when
FIGURE 7.1 Structure of Fullerene C60 Molecule. [Reprinted with permission from Rondags
et al., (2017)] [6].

184 Carbon-Based Nanocarriers for Drug Delivery
dissolving in toluene, becomes pink [4]. The Buckyballs polymerize when exposed to
intense UV light, responsible for binding between nearby balls. C60 does not dissolve
in toluene after it has polymerized [11]. The free rotation has been seen at normal
temperatures in NMR investigations of C60 benzene solvates. The balls are in their
crystalline orientations and spinning freely at around -13o [4]. Their motions start to
become restricted to particular directions at lower temperatures. The balls subsequently get fully struck below 183o [12]. Chemically, the molecule is highly stable;
temperatures exceeding 1000 oC are needed to split the balls. Fullerenes may be
converted to graphite by roasting them to 1500 oC in the absence of air. In addition
to C60, fullerenes can include between 30 and 980 carbon atoms, generating various
congurations with various characteristics and application areas.
The fundamental soccer ball conguration starts to lose roundness when hexagons are introduced or subtracted. C70, which comprises 25 hexagons, has a rugby
ball-like form. The form of giant fullerenes is pentagonal. Asteroids resemble
smaller fullerenes. Loss of stability results from the loss of roundness, with C60
proving to be the most stable of all. In addition to C60 and C70, C76, C78, C84, and
C86 have all been isolated and thoroughly researched. Diamond has a higher density
than fullerenes (3.51 g/cc against 1.65 g/cc). Fullerenes are water-insoluble. Toluene,
o-dichlorobenzene, xylene, and carbon disulde are effective solvents [13,14]. Yellow
to yellowish-green colors can be seen in thin layers of fullerenes.
Several chemical variations of fullerenes were identied soon after their discovery (Figure7.2) [4]. The following are a few notable fullerene species.
7.2.1 alkali-DopeD FUllerenes
Being extremely electronegative, fullerene molecules easily combine with elements
that provide electrons, most frequently alkali metals [15]. By lling up the gap
FIGURE 7.2 Chemical Modications of Fullerene [4].

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among Buckyballs and giving the nearby C60 molecule a valence electron, alkali
metal atoms from this reaction producean intriguing family of compounds known
as alkali-doped fullerides. When potassium or rubidium make up the alkali atoms,
the resulting compounds—such as K3C60 and Rb3C60—are known as superconductors because they conduct electricity even without resistance at temperatures below
20–40 K [16].
7.2.2 enDoheDral FUllerenes
It is feasible to contain another atom inside of fullerenes since they have a hollow
interior and a closed shell of carbon atoms. This subclass of fullerene derivatives is
called endohedral fullerenes. They are called metallofullerenes once the entrapped
element is a metal [17]. Even though C60 is the most prevalent fullerene, only a tiny
number of endohedral compounds have indeed been developed utilizing C60 as the
framework. C82, C84, or even higher fullerenes are used to make the majority of
endohedral materials. In addition to a few of the noble gases, lanthanum, yttrium,
scandium, and other elements can combine to produce stable endohedral compounds
[18]. Endohedral material should be formed concurrently with the construction of the
cage since it is extremely hard to break up carbon cage molecules to encapsulate a
foreign atom inside of them [19].
7.2.3 eXoheDral FUllerenes
Exohedral fullerenes, also known as fullerene derivatives, are compounds produced
by a chemical interaction between fullerenes and perhaps other chemical groups.
They are the most signicant and useful of all fullerene species.
The term “functionalized fullerenes” also refers to fullerene derivatives. As a consequence of the conjugated π-system of electrons that fullerenes have, there are two
basic chemical transformations that may occur on their surface: addition reactions
and redox reactions, which result in covalent exohedral adducts and salts, respectively [20]. Many fullerene derivatives have been developed with enhanced solubility
proles since fullerenes are insoluble in water.
7.2.4 heTeroFUllerenes
A further important class of altered fullerenes is the heterofullerenes. These are
hetero-analogs of fullerenes with carbon counts of 60 and more; one or more carbon
atoms in the cages are replaced with heteroatoms, such as trivalent nitrogen or boron
atoms. Aza (60) fullerene C59N and its dimer (C59N)2 are the most basic nitrogen
fullerene derivatives [21].
7.3 FULLERENE AS A DRUG CARRIER: SIGNIFICANCE
AND PROSPECTS
Fullerenes are chemically inert, hollow, and innitely adjustable. They are not
digested when given orally in the water-soluble form, but when given as an intravenous injection, they are quickly disseminated to numerous bodily regions and
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