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activities and the extracellul ar environment, such temperature changes inside cells
are usually on a small scale and transient, making them difficult to measure. As a result, developing customized thermo-responsive CDs carriers based on these internal
temperature differences remains uncertain. Along these lines, heat-susceptible carriers can be created by using an external heat source [81]. Exogenous stimuli, such as
photo- and ultrasound-responsive NPs that destabilize when exposed to a specific
wavelength of light, were also explored. Many studies have emphasized the delivery
of drugs via dual- or multi-responsive nanocarriers, with the combination of stimuli
working synergistically and methodically for efficient drug release, such as pH/redox-,
pH/enzyme-, and pH/light-responsive drug carriers [79].
13.7.1 Stimuli-responsive drug release from CDs
13.7.1.1 pH stimuli-responsive drug release
pH discrepancy is prevalent in many parts of the human body as summarized in
Table 13.3, and is critical to CDs’ functionality and often explored for controlled drug
release. This distinction, particularly the lower pH levels in tumour cells under certain conditions such as increased glycolic pathway and lactic acid production, has
been used to develop pH-sensitive CDs. These pH susceptibilities were processed
through the disruption of certain bonds that the CDs are equipped with, resulting in
the release of the drug that is normally protected under physiological environment.
Evidently, DOX release from CD–DOX was higher at lower pH (pH 5.0, 82%) compared
to pH 6.8 and 7.4 [10].
Table 13.3: pH pertaining to
different human body parts.
Body part pH
Stomach –
Colon
Lysosomes .–
Endosomes .–
Cytosol .
pH sensing is considered a highly beneficial property of CDs. CD–DOX pH-responsive
nanoconjugate resulted in approximately 12% of the DOX released from the CDs in vitro
at pH 7.2, while 4% of the drug was released at pH 5.8. Using a pH that mimics the tumour environment as a trigger for drug release ensures that the drug reaches the target
site in its intact form and that the drug effects are confined to the tumour site [82]. In a
similar strategy, DOX loaded in HCDs demonstrated an improved DOX release profile
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from HCD-based nanocarriers at pH 5.0 which mimics the acidic environment of intracellular lysosomes when compared to the physiological environment (pH 7.4). The HCD
nanocarriers only released 4% of the drug at pH 7.4, while 70% of the drug was released
at pH 5.0 [70]. The CDs produced from Daucus carota subsp. sativus (carrot) roots used
hydrogen bonding to couple mitomycin, a chemotherapy drug used to treat cancers;
breakage of the hydrogen bonding at the mildly acidic tumour extracellular microenvironment (pH ~ 6.80) caused the release of mitomycin [83].
CDs@MSN-DOX nanohybrid also demonstrated the ability to increase DOX release
under slightly acidic conditions (pH 5.0) at 37 °C. The CDs@MSN-DOX nanohybrid was
internalized by HeLa cells after 2 h and was found primarily in the lysosomes, where
the low pH (pH 5.0) triggered DOX release from the nanocarrier, resulting in cell death
[84]. CD–DOX resulting from electrostatic interaction between positively and negatively
charged functional groups on CDs and DOX also dissociated as the pH value decreased.
The carboxyl groups on the surface of CDs were gradually protonated, and the electrostatic interaction between DOX and CDs was gradually weakened, increasing the rate
and amount of DOX released [71]. The surface charge of the CDs can be controlled using
pH. This behaviour has been reported to alter drug release at different pH levels. pHresponsive CDs were produced by modifying their surface with zwitterionic molecules,
which have a positive charge at low or acidic pH and change to a negative charge when
exposed to high or basic pH. As a result of the CDs changing conformation in the acidic
environment of the tumour cells (pH 6.5–6.9), the therapeutic agents were released [38,
85]. Notably, the CDs-MSN nanohybrid loaded with DOX and capped with a zwitterionic
antibiofouling layer allowed DOX release when subjected to a pH of the tumour extracellular fluid. In this way, DOX release was controlled and occurred only at pH 6.8 after
enzymatic removal of polycaprolactone (PCL); the MSN gate keeper prevented early
drug release. This was evident because nothing happened for 5 days, and when esterase
was added on day six, 90% of the drug was released within 3 days. To prove that the
DOX release was dependent on both pH and enzyme, when the MSN-CDs were subjected
to pH 7.4 in the presence of the enzyme or pH 6.8 buffer without the enzyme, ~ 15% of
the drug was released after 28 days [38].
In addition to chemotherapy, CDs can be used to deliver and release other therapeutic agents such as antibiotics [54, 55] and antipsychotic drug [53]. CD-coated alginate
beads (CA-CDs) were produced by electrostatic interactions between the positively
charged CDs and negatively charged alginate, and used as nanocarriers for tetracycline
(TC) and TC associated with β-cyclodextrin. After 96 h at pH 1, the CA-CDs released 70%
of TC, indicating their applicability in the gastrointestinal tract [54]. In another study,
CDs loaded with the broad-spectrum antibiotic ciprofloxacin (Cipro@CDs) could release
the antibiotic under physiological conditions (pH 7.4); the release profile was sustained
for 24 h. Cipro@CDs demonstrated time-dependent and controlled release of Cipro as
well as potent antibacterial activity against both gram-positive and gram-negative
strains [55]. Furthermore, CDs were used to deliver HaLO; a constant HaLO release
from the nanocarrier was achieved for more than 40 h under physiological conditions
300 Nicole Remaliah Samantha Sibuyi et al.
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(pH 7.4). The HaLO release profile from CDs was found to have an initial burst in the
first 4–5 h, followed by a sustained release for up to 40 h [53].
13.7.1.2 Redox stimuli-responsive drug release
Normal cells have a significantly lower redox potential than tumour cells, and this difference exists between the intracellular and extracellular environments. The cellular
redox environment is known to be primarily regulated by GSH levels. GSH is a thiol
compound found in high concentrations, ranging between 5 and 10 mM, in the cytoplasm of mammalian cells. GSH deficiency always increases susceptibility to oxidative
stress, whereas GSH excess generally increases antioxidant capacity and oxidative
stress resistance [79]. As a result, intracellular GSH may be a promising stimulus for
triggering drug release from CDs.
A redox-responsive MSN capped by fluorescent CDs showed controlled DOX release by exploiting their sensitivity towards the intracellular GSH. The CDs that were
electrostatically anchored onto the surface of the MSNs blocked the pores of the MSNs
and prevented the leakage of DOX. When GSH was added to the physiological environment, the integrity of the system was disrupted due to the breakage and detachment
of the disulphide bonds, resulting in the rapid release of DOX [86].
13.7.1.3 Temperature stimuli-responsive drug release
CDs are often used with other systems to create thermo-responsive nanohybrid carriers; most times, thermosensitive polymers such as poly(N-isopropyl acrylamide) and
poly(methyl vinyl ether) [2] and other nanosystems [87] are used in conjugation with
CDs to prevent drug leakage and ensure controlled release. A thermo-responsive CDhydrogel nanocarrier for diclofenac demonstrated controlled drug release mediated by
an external source. Drug release relied on the thermo-susceptible hydrogels after topical administration in the eyes of the rabbits. CDs fluorescent in various ocular tissues
(cornea, crystalline lens, sclera, and conjunctiva) was an indication that diclofenac was
distributed in these tissues [87]. Thus, in situ or external temperature variation from
other systems, and not directly from the CDs, can also be exploited in the development
of thermo-responsive CD-based DDS.
13.7.1.4 Light stimuli-responsive drug release
Light-responsive DDS that operate at different wavelengths have been reported. UV
light has poor tissue penetration, so it is generally replaced by NIR wavelengths,
which not only ensure better tissue penetration but are also safe for in vivo use [88].
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Owing to the intrinsic photothermal conversion ability of CDs, NIR laser irradiation
could also be used to enhance drug release from the nanocarriers. The increase in
temperature in the local tissues will help with the detachment of the drug. CD–DOX
exhibited strong absorbance in the NIR region with higher photothermal conversion
efficiency. The NIR light-stimulated DOX release, allowing for drug accumulation in
the cancer cells, and increasing the drug’s effectiveness in killing the cancer cells.
Wang et al. created a CD– -nanohybrid loaded with DOX; the nanohybrid was composed of magnetic iron oxide (Fe
) nanocrystals and fluorescent CDs, with the Fe3O
3O4
nanocrystals clustered in the core and the CDs implanted in the porous carbon shell.
DOX release profile from Fe
@CDs was monitored in the dark und er NIR irradia-
3O4
tion. The kinetics of DOX release from the nanocarrier proceeded slowly and almost
steadily. Irradiation with NIR light significantly increased the rate of DOX release
from the hybrid nanocarrier [89].
Another photo-responsive system, the nitrogen-doped and PEG200-coated CDs initiated delivery of DOX in human breast cancer (MCF-7) cells via NIR two-photon excitation.
Under NIR laser irradiation, DOX was successfully released from the CDs, subsequently
contributing to enhanced cell death. These findings implied that NIR could be used to
control the rate of DOX release from the CD nanocarriers [90]. Other light sources have
been investigated in addition to NIR irradiation. Qucbl-CDs demonstrated light-controlled
−2
drug release mediated by W light (≥365 nm, Hg-vapour lamp, 120 mW cm
−2
laser (5 mW cm
). Approximately 73% and 20% of Qucbl was released after 30 min of
)andHe–Ne
irradiation with W light and He–Ne laser, respectively [91].
4
13.7.1.5 Multiple stimuli-responsive CDs for drug release
To create potent formulatio ns, multiple stimuli-responsive agents have been used to
trigger drug release. These triggers can be a combination of endogenous stimuli, exogenous stimuli, or a combination of both endogenous and exogenous stimuli. This is
currently being investigated to improve the efficiency of these systems [92]. pH- and
enzyme-responsive CD-MSN-DOX hybrid relied on the tumour pH to remove the zwitterionic layer that prevented formation of protein corona on the surface, and the esterases to degrade the PCL and release DOX from the MSNs. The low pH was the first
and vital trigger which then allowed esterase an access to the PCL and controlled DOX
release. On the contrary, the enzyme at high pH conditions failed to degrade the PCL
and no drug release was observed, thus indicating a highly selective drug release performance to tumour tissue [38].
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13.8 Biocompatibility and cytotoxicity of CDs
CDs are smaller in size, with a diameter less than 10 nm and can easily interact with various cellular organelles and induce cellular damage. They are presumed to be biocompatible and have reduced toxicity compared to other QDs synthesized from semiconducting
materials [93] and toxic metal compounds, because they are synthesized from carbon,
one of the building blocks of nature [56, 94, 95]. Thus, CDs are biocompatible and safer
for the living organisms and the environment. Several in vitro and in vivo studies have
been done to evaluate the toxicity of CDs using mammalian (normal vs cancerous) cell
lines, as well as animal models with remarkable results. The biocompatibility and safety
of CDs are dependent on factors such as the methods of synthesis, surface composition,
and surface charge. CDs synthesized through hydrothermal methods were shown to be
non-toxic to normal breast (MCF-10A) cell line compared to calcination- and microwavebased CDs. The latter showed time-dependent cytotoxicity effects, while the hydrothermal synthesized CDs remained non-toxic up to 72 h at concentrations ≤4mgmL
CDs synthesized by the hydrothermal treatment of folic acid and kappa-carrageenan
(FKC-CDs) had negligible haemolytic effect of 2.71% (haemolysis values <10% are in the
–1
accepted range) at 600 μgmL
FKC-CDs up to 600 μgmL
, and thus have good overall blood biocompatibility. The
–1
showed no visible reduction in the viability of HeLa and normal fibroblast cells, suggesting that the FKC-CDs have no cytotoxic and no anticancer activities [97]. CDs synthesized by the hydrothermal treatment of
phenylenediamine with
p-
various metal ions as catalysts produced non-toxic CDs: pPCDs, Ag−pPCDs, Cu−pPCDs,
Pt−pPCDs, Fe−pPCDs, Pd−pPCDs, and Ni−pPCDs. The metal ions were undetected in the
final products, and the CDs were considered as biocompatible as they did not contain
metal elements which tend to be cytotoxic. Out of all the CDs, the Ni−pPCDs showed
better phy sicochemical and PL properties than the rest, with cell viabilities ~ 80%
–1
at ≤50 μgmL
of Ni−pPCDs in both normal (AT II) and lung cancer (A549) cells. In a
mouse model, the Ni−pPCDs accumulated mostly in the tumour site and had no notable
accumulation in the major organs such as the heart, liver, spleen, lungs, and kidneys
[98]; further certifying the biocompatibility of the CDs. Many other studies also demonstrated the non-cytotoxic nature of CDs synthesized through different methods in both
normal and cancer cell lines [93, 99–101]. The unloaded CDs did not show any toxicity
on both normal (HL-7702, H9C2, HUVEC) and cancer (HeLa, HepG2, MCF-7) cells at con-
–1
centrations up to 100 µg mL
from 0–96 h [3]. Similarly, CDs were shown to have no
cytotoxic effects on the mouse fibroblast (L929) and MCF-7 cells at concentrations up to
0.5 mg per mlat 24 and 48 h [10].
–1
[96].
13.8.1 Selective toxicity of drug-loaded CDs
Due to their non-cytotoxic and biocompatible nature, CDs were used in drug delivery
applications to improve the performance and the therapeutic index of certain drugs.
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Anticancer drugs such as DOX are non-selective in their action towards both cancer
and normal cells. However, when they are loaded into CDs their cytotoxicity to normal cells was significantly reduced, while their anticancer activity was enhanced. To
demonstrate this effect, the D OX-loaded CDs (CD–DOX) compared to unloaded CDs
–1
had no cytotoxic effect in L929 cells at ≤600 µg mL
for 24–72 h of treatment. The unloaded CDs had negligible cytotoxicity towards L929 cells, while the free DOX and the
CD–DOX at 1.5 μM DOX showed differential activities. The free DOX significantly reduced cell viability in the L929 cells compared to the treatment with the CD–DOX at
all the time points. This suggested that the cytotoxic effect of DOX was reduced when
it was loaded into the CDs and could potentially mean that the side effects exhibited
by free DOX onto normal cells can be minimized when the drug is loaded on CDs.
Also, in the cancerous ACC-2 cells, CD–DOX exhibited a higher antitumor activity than
free DOX at all the time points. This effect was more pronounced in the 72 h treatment
resulting in 5% ACC-2 cell viability after treatment with the CD–DOX. The antitumor
effect as well as the minimal cytotoxicity effect was attributed to the slow release of
DOX from the CD– DOX [95]. Similarly, in an other study, CD–DOX at ≤500 µg mL
–1
showed no cytotoxic effect in the L929 cells at all time points. Moreover, no notable
cytotoxicity or anticancer activity was observedinboththeL929andMCF-7cells
treated with the unloaded CDs, at all investigated concentrations and time points. On
the contrary, free DOX and CD–DOX reduced the viability of the MCF-7 cells. The reduction was more pronounced in the CD–DOX treatments compared to the free DOX,
with the IC
tively, which were further reduced to be 0.652 and 0.356 µg mL
values of 0.983 and 0.939 µg mL–1of free DOX at 24 and 48 h, respec-
50
–1
at 24 and 48 h for
CD–DOX, respectively [10].
The cytotoxicity of CD–DOX was reported to be time- and concentration-dependent,
and showed similar or superior effects to free DOX. Their effects were significant from
–1
0.0625 µg mL
at 24 h and increased to 0.15625 µg mL–1at 48 h for the CDs-DOX in the
cancer cells. Both the unloaded CDs and CD–DOX were shown to be equally taken in by
the normal and cancer cells, and the CDs were able to offer some protection to the noncancer cells. Their cytotoxicity was significantly reduced than that of free DOX [3]. The
cytotoxicity of the CDs is also dependent on their biodistribution. Large amounts of
CD–DOX intravenously injected in HepG2 tumour-bearing mice were located by the CDs
fluorescence in the tumour and the kidneys after 24 h, with negligible amounts in the
liver, spleen, heart, and lungs. This was an indication that the nanomaterials have some
degree of biocompatibility and could be safe to use in vivo [3]. The CDs might not have
long-term toxic effects on mice, as the histological analysis of vital tissues at the baseline, 7 and 21 days showed no changes in the morphology of these tissues [9].
The selectivity of drug-loaded CDs was also reported for other drugs such as epirubicin, temozolomide [102], mitoxantrone (MTO) [103], coptisine [94], and FAC [56]. In
these four studies, it was evident that unloaded CDs had no cytotoxicity against the test
cell lines, normal and diseased alike. The drug-loaded CDs also demonstrated some selective toxicity towards diseased cells [94, 102, 103]; with the exception of CD–FAC [56]
304 Nicole Remaliah Samantha Sibuyi et al.
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and CD–temozolomide [102] which were non-toxic to both normal and diseased cells.
Moreover, the drug-loaded CDs showed a significant cytotoxic effect on the cells than
the free drugs in a dose-dependent manner [84, 93, 94]. In vivo studies showed no apparent changes in the size of the tumour as well as the weight of the mice treated with
both free coptisine and CD-coptisine, indicating their biocompatibility and non-toxic effect. Furthermore, the CD-coptisine only accumulated in the tumour site as opposed
to other organs such as the spleen, heart, kidneys, and liver, further confirming the
biocompatibility and non-toxic nature of the CD-coptisine [94]. In a study by Hettiarachchi et al., multi-drug (epirubicin and temozolomide)-loaded CDs with or without
targeting moiety (transferrin) compared to single drug-loaded-CDs with or without
transferrin and the free drugs had enhanced cytotoxicity towards several cancerous
(SJGBM2, CHLA266, CHLA200, and U87) cells lines. Of the single drug-loaded-CDs,
only the CD-epirubicin reduced cell viabilitiesto17%and30%inallcellsat10μM
while the CD-temozolomide had no notable cytotoxic effect at all tested concentrations in all the cancer cells. A targeting ligand (transferrin) enhanced the efficacy of
the drug-loaded CDs even at lower drug concentrations [102].
From these studies, it is quite evident that decorating CDs with various biomolecules can improve the selectivity of the CDs as well as the performance and delivery
of the loaded drug [104]. Functionalization of CD–DOX with 4-carboxybenzylboro nic
acid (CBBA; DOX/CBBA-CDs) reduced the cell viability in a concentration-dependent
manner in HeLa cells, while the unloaded CDs and CBBS-CDs were non-cytotoxic up to
–1
400 µg mL
[71]. Furthermore, the use CDs with other DDS was shown to improve the
delivery, performance, biocompatibility, and efficacy of the drugs. This was demonstrated by a CDs nanohybrid containing hyaluronic acid, disulphide bonds, and hMSNs
(hMSN-SS-CD
@HA) for the delivery of DOX. The hMSN-SH and hMSN-SS-CD
PEI
PEI
@HA
had no notable cytotoxic effect on both normal mouse fibroblast (NIH-3T3) and A549
cells. The hMSN-SS-CD
@ showed selectivity cytotoxicity towards the cancer cells
PEI
[105]. A number of studies can attest to the non-toxicity and potential biocompatibility
of the unloaded CDs, and their ability to enhance drug effects.
13.9 Conclusion
CDs hold promise as an effective DDS, mainly due to the fact that they are made from
biocompatible carbon precursors. Moreover, their exceptional physicochemical properties encourage their dual bio-applications for construction of smart diagnostic and therapeutic agents. CDs have been timeously proven to be non-toxic an d biocompatible
towards cells and animals. These desirable properties make CDs excellent DDS. They
can transport their cargoes without exhibiting any bystander effects on neighbouring
cells. Their flexibility to encapsulate or load drugs on their surface is especially appealing and can be exploited for multiplexing. Additionally, CDs can be tailored to be
Chapter 13 Carbon dots in drug delivery 305
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stimuli-responsive and only release their cargoes in specified targets for more control
over the drug kinetics. Thus, CDs as DDS can minimize bystander effects on the normal
cells while inhibiting the growth and killing the targeted cells. All these events can be
monitored in real time due to their PL and fluorescent prop erties. However, much
work remains to be done to translate this technology into clinically viable systems.
References
[1] Svenson S. Carrier-Based Drug Delivery, 2004, 2–23. https://doi.org/10.1021/BK-2004-0879.CH001.
[2] Adepu S, Ramakrishna S, Costa-Pinto R, Oliveira AL. Controlled drug delivery systems: current status
and future directions. Mol. 2021, 26, 5905. https://doi.org/10.3390/MOLECULES26195905.
[3] Zeng Q, Shao D, He X, Ren Z, Ji W, Shan C, Qu S, Li J, Chen L, Li Q. Carbon dots as a trackable
drug delivery carrier for localized cancer therapy: In vivo. J Mater Chem B. 2016, 4, 5119–5126.
https://doi.org/10.1039/C6TB01259K.
[4] Liu D, Yang F, Xiong F, Gu N. The smart drug delivery system and its clinical potential. Theranostics.
2016, 6, 1306–1323. https://doi.org/10.7150/THNO.14858.
[5] Amer Ridha A, Pakravan P, Hemati Azandaryani A, Zhaleh H, Carbon dots; the smallest
photoresponsive structure of carbon in advanced drug targeting. J Drug Deliv Sci Technol, 2020, 55.
https://doi.org/10.1016/J.JDDST.2019.101408.
[6] Zhao MX, Zhu BJ. The research and applications of quantum dots as nano-carriers for targeted
drug delivery and cancer therapy. Nanoscale Res Lett. 2016, 11, 1–9. https://doi.org/10.1186/s11671016-1394-9.
[7] Phillips MA, Gran ML, Peppas NA. Targeted nanodelivery of drugs and diagnostics. Nano Today.
2010, 5, 143–159. https://doi.org/10.1016/j.nantod.2010.03.003.
[8] Xia J, Kawamura Y, Suehiro T, Chen Y, Sato K. Carbon dots have antitumor action as monotherapy or
combination therapy. Drug Discov Ther. 2019, 13, 114–117. https://doi.org/10.5582/DDT.2019.01013.
[9] Sun Y, Zheng S, Liu L, Kong Y, Zhang A, Xu K, Han C. The cost-effective preparation of green
fluorescent carbon dots for bioimaging and enhanced intracellular drug delivery. Nanoscale Res
Lett. 2020, 15, 1–9. https://doi.org/https://doi.org/10.1186/s11671-020-3288-0.
[10] Kong T, Hao L, Wei Y, Cai X, Zhu B. Doxorubicin conjugated carbon dots as a drug delivery system
for human breast cancer therapy. Cell Prolif. 2018, 51. https://doi.org/10.1111/CPR.12488.
[11] Sultana A, Zare M, Thomas V, Kumar TSS, Ramakrishna S. Nano-based drug delivery systems:
Conventional drug delivery routes, recent developments and future prospects. Med Drug Discov.
2022, 15, 100134. https://doi.org/10.1016/J.MEDIDD.2022.100134.
[12] Homayun B, Lin X, Choi H-J. pharmaceutics challenges and recent progress in oral drug delivery
systems for biopharmaceuticals. 2019. doi: https://doi.org/10.3390/pharmaceutics11030129.
[13] Kerz T, Paret G, Herff H. Routes of drug administration. Card Arrest Sci Pract Resusc Med. 2007,
614–638. https://doi.org/10.1017/CBO9780511544828.035.
[14] Norouzi M, Nazari B, Miller DW. Injectable hydrogel-based drug delivery systems for local cancer
therapy. Drug Discov Today. 2016, 21, 1835–1849. https://doi.org/10.1016/J.DRUDIS.2016.07.006.
[15] Escobar-Chavez J, Diaz-Torres R, Rodriguez-Cruz IM, Domínguez-Delgado S-M, Angeles-Anguiano
M-C. Nanocarriers for transdermal drug delivery. Res Reports Transdermal Drug Deliv. 2012, 3.
https://doi.org/10.2147/rrtd.s32621.
[16] Rau JL, Faarc R. The inhalation of drugs: Advantages and problems introduction: the inhalation of
drugs for respiratory disease. Respir Care. 2005, 50, 367–382.
306 Nicole Remaliah Samantha Sibuyi et al.
https://t.me/medicina_free
[17] Saleem K, Khursheed Z, Hano C, Anjum I, Anjum S, Applications of nanomaterials in leishmaniasis:
A focus on recent advances and challenges, Nanomaterials. 2019, 9. https://doi.org/10.3390/
NANO9121749.
[18] Felice B, Prabhakaran MP, Rodr íguez AP, Ramakrishna S. Drug delivery vehicles on a
nano-engineering perspective. Mater Sci Eng C: Mater Biol Appl. 2014, 41, 178–195. https://doi.org/
10.1016/J.MSEC.2014.04.049.
[19] Bartosova L, Bajgar J. Transdermal drug delivery in vitro using diffusion cells. Curr Med Chem. 2012,
19, 4671–4677. https://doi.org/10.2174/092986712803306358.
[20] De Jong WH, Borm PJA. Drug delivery and nanoparticles: Applications and hazards. Int J
Nanomedicine. 2008, 3, 133. https://doi.org/10.2147/IJN.S596.
[21] Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, Wu S, Deng Y, Zhang J, Shao A. Nanoparticle-based drug
delivery in cancer therapy and its role in overcoming drug resistance. Front Mol Biosci. 2020, 7, 193.
https://doi.org/10.3389/FMOLB.2020.00193.
[22] Souto EB, Souto SB, Campos JR, Severino P, Pashirova TN, Zakharova LY, Silva AM, Durazzo A,
Lucarini M, Izzo AA, Santini A. Nanoparticle delivery systems in the treatment of diabetes
complications. Molecules. 2019, 24, 4209. https://doi.org/10.3390/MOLECULES24234209.
[23] Munasinghe E, Aththapaththu M, Jayarathne L. Magnetic and quantum dot nanoparticles for drug
delivery and diagnostic systems. Colloid Sci Pharm Nanotechnol. 2020. https://doi.org/10.5772/
INTECHOPEN.88611.
[24] Qi L, Gao X. Emerging application of quantum dots for drug delivery and therapy. Expert Opin Drug
Deliv. 2008, 5, 263–267. https://doi.org/10.1517/17425247.5.3.263.
[25] Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, Diaz-Torres LA,
Grillo R, Swamy MK, Sharma S, Habtemariam S, Shin HS. Nano based drug delivery systems:
Recent developments and future prospects. J Nanobiotechnol. 2018, 16, 71. https://doi.org/10.1186/
s12951-018-0392-8.
[26] Wu W, Arsene AL. Drug carriers: Classification, administration, release profiles, and industrial
approach. Process. 2021, 9, 470. https://doi.org/10.3390/PR9030470.
[27] Tan A, Wang Z, Lust R, Hua S, Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK. Advances and
challenges of liposome assisted drug delivery. Front Pharmacol. 2015, Www.Frontiersin.Org, 6, 286.
https://doi.org/10.3389/fphar.2015.00286.
[28] Rossi F, Sharon M, Irudayaraj J, Vega-Vásquez P, Mosier NS. Nanoscale drug delivery systems:
From medicine to agriculture. Front Bioeng Biotechnol. 2020, Www.Frontiersin.Org, 8, 79.
https://doi.org/10.3389/fbioe.2020.00079.
[29] Mourya VK. Polymeric micelles: General considerations and their applications. Indian J Pharm
Res Educ. 2011, 45, https://doi.org/Nillz.
[30] Lu Y, Zhang E, Yang J, Cao Z. Strategies to improve micelle stability for drug delivery. Nano Res.
2018, 11, 4985–4998. https://doi.org/10.1007/s12274-018-2152-3.
[31] Sibuyi NRS, Moabelo KL, Fadaka AO, Meyer S, Onani MO, Madiehe AM, Meyer M. Multifunctional
gold nanoparticles for improved diagnostic and therapeutic applications: A review. Nanoscale
Res Lett. 2021, 161(16). 1–27. https://doi.org/10.1186/S11671-021-03632-W.
[32] Jahangirian H, Lemraski EG, Webster TJ, Rafiee-Moghaddam R, Abdollahi Y. A review of drug
delivery systems based on nanotechnology and green chemistry: Green nanomedicine. Int J
Nanomedicine. 2017, 12, 2957–2978. https://doi.org/10.2147/IJN.S127683.
[33] Inglut CT, Sorrin AJ, Kuruppu T, Vig S, Cicalo J, Ahmad H, Huang HC. Immunological and
toxicological considerations for the design of liposomes. Nanomaterials. 2020, 10. https://doi.org/
10.3390/NANO10020190.
[34] Chu KW, Lee SL, Chang CJ, Liu L. Recent progress of carbon dot precursors and photocatalysis
applications. Polym. 2019, 11, 689. https://doi.org/10.3390/POLYM11040689.
Chapter 13 Carbon dots in drug delivery 307
https://t.me/medicina_free
[35] Probst CE, Zrazhevskiy P, Bagalkot V, Gao X. Quantum dots as a platform for nanoparticle drug delivery
vehicle design. Adv Drug Deliv Rev. 2013, 65, 703–718. https://doi.org/10.1016/j.addr.2012.09.036.
[36] Aguilar Cosme JR, Bryant HE, Claeyssens F. Carbon dot-protoporphyrin IX conjugates for improved
drug delivery and bioimaging. PLoS One. 2019, 14, e0220210. https://doi.org/10.1371/JOURNAL.
PONE.0220210.
[37] Haque Adrita S, Nujhat Tasnim K, Hyun Ryu J, Md Sharker S, Ki Choi S. Nanotheranostic carbon dots
as an emerging platform for cancer therapy. n.d. https://doi.org/10.3390/jnt1010006.
[38] Liu Z, Chen X, Zhang X, Gooding JJ, Zhou Y. Carbon-quantum-dots-loaded mesoporous silica
nanocarriers with pH-switchable zwitterionic surface and enzyme-responsive pore-cap for targeted
imaging and drug delivery to tumor. Adv Healthc Mater. 2016, 5, 1401–1407. https://doi.org/
10.1002/ADHM.201600002.
[39] Fasipe O. Recent advances and current trend in the pharmacotherapy of obesity. Arch Med Heal Sci.
2018, 6, 99. https://doi.org/10.4103/amhs.amhs_30_18.
[40] Li S, Peng Z, Dallman J, Baker J, Othman AM, Blackwelder PL, Leblanc RM. Crossing the
blood–brain–barrier with transferrin conjugated carbon dots: A zebrafish model study. Coll Surf
B: Biointerfac. 2016, 145, 251–256. https://doi.org/10.1016/J.COLSURFB.2016.05.007.
[41] Zhou Y, Mintz KJ, Cheng L, Chen J, Ferreira BCLB, Hettiarachchi SD, Liyanage PY, Seven ES,
Miloserdov N, Pandey RR, Quiroga B, Blackwelder PL, Chusuei CC, Li S, Peng Z, Leblanc RM. Direct
conjugation of distinct carbon dots as Lego-like building blocks for the assembly of versatile drug
nanocarriers. J Colloid Interface Sci. 2020, 576, 412–425. https://doi.org/10.1016/J.JCIS.2020.05.005.
[42] Sharma SK, Micic M, Li S, Hoar B, Paudyal S, Zahran EM, Leblanc RM, Conjugation of carbon dots
with β-galactosidase enzyme: surface chemistry and use in biosensing, Mol 2019, 24, 3275.
https://doi.org/10.3390/MOLECULES24183275.
[43] Zhou Y, Chen X, Cao J, Gao H. Overcoming the biological barriers in the tumor microenvironment
for improving drug delivery and efficacy. J Mater Chem B. 2020, 8, 6765–6781. https://doi.org/
10.1039/D0TB00649A.
[44] Sriraman SK, Aryasomayajula B, Torchilin VP. Barriers to drug delivery in solid tumors. Tissue
Barriers. 2014, 2, e29528-1-e29528-10. https://doi.org/10.4161/TISB.29528.
[45] Baghban R, Roshangar L, Jahanban-Esfahlan R, Seidi K, Ebrahimi-Kalan A, Jaymand M, Kolahian S,
Javaheri T, Zare P. Tumor microenvironment complexity and therapeutic implications at a glance.
Cell Commun Signal. 2020, 18(1), 1–19. https://doi.org/10.1186/S12964-020-0530-4.
[46] Blakeley J. Drug delivery to brain tumors. Curr Neurol Neurosci Rep. 2008, 8, 235. https://doi.org/
10.1007/S11910-008-0036-8.
[47] Arvanitis CD, Ferraro GB, Jain RK. The blood–brain barrier and blood–tumour barrier in brain
tumours and metastases. Nat R ev Cancer. 2019, 201(20), 26–41. https://doi.org/10.1038/s41568019-0205-x.
[48] Calabrese G, De Luca G, Nocito G, Rizzo MG, Lombardo SP, Chisari G, Forte S, Sciuto EL, Conoci
S. Carbon dots: An innovative tool for drug delivery in brain tumors. Int J Mol Sci. 2021, 22.
https://doi.org/10.3390/IJMS222111783.
[49] Zhou Y, Liyanage PY, Devadoss D, Rios Guevara LR, Cheng L, Graham RM, Chand HS, Al-Youbi AO,
Bashammakh AS, El-Shahawi MS, Leblanc RM. Nontoxic amphiphilic carbon dots as promising
drug nanocarriers across the blood–brain barrier and inhibitors of β-amyloid. Nanoscale. 2019, 11,
22387–22397. https://doi.org/10.1039/C9NR08194A.
[50] Ashrafizadeh M, Mohammadinejad R, Kailasa SK, Ahmadi Z, Afshar EG, Pardakhty A, Carbon dots as
versatile nanoarchitectures for the treatment of neurological disorders and their theranostic
applications: A review. Adv Colloid Interface Sci. 2020, 278. https://doi.org/10.1016/J.
CIS.2020.102123.
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