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Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics
With the development of the latest technologies, scientists are looking to design novel strategies for the treatment and diagnosis of cancer. Advances in medicinal plant research and nanotechnology have attracted many researchers to the green synthesis of metallic nanoparticles due to its several advantages over conventional synthesis (simple, fast, energy efficient, one pot processes, safer, economical and biocompatibility). Medicinally active plants have proven to be the best reservoirs of diverse phytochemicals for the synthesis of biogenic silver nanoparticles (AgNPs). In this review, we discuss mechanistic advances in the synthesis and optimization of AgNPs from plant extracts. Moreover, we have thoroughly discussed the recent developments and milestones achieved in the use of biogenic AgNPs as cancer theranostic agents and their proposed mechanism of action. Anticipating all of the challenges, we hope that biogenic AgNPs may become a potential cancer theranostic agent in the near future. First draft submitted: 20 July 2016; Accepted for publication: 26 September 2016; Published online: 4 November 2016 Keywords: ANTICANCERACTIVITYsBIOGENICNANOPARTICLESsCANCERTHERANOSTICSsGREEN CHEMISTRYsGREENSYNTHESISsNANOMEDICINEsPHYTOSYNTHESISsSILVERNANOPARTICLES
Cancer: a global menace Cancer is caused by mutations in genes that trigger a series of events on the molecular level, eventually leading to tumor formation. A cancerous state is described by uncontrolled cell division and subsequent invasions of healthy cells and tissues [1] . Cancer is one of the major risk factors of morbidities and mortalities all over the world. The American Cancer Society anticipates that the global burden of cancer will upsurge to 21.7 million fresh cases by the year 2030 [2] . According to a report published by iMShealth Institute for Healthcare Informatics in June 2016, the global market for cancer treatments grew to a record level of US$107 billion in 2015, and is expected to reach US$150 billion by 2020 [3] . It is estimated that one out of eight deaths is the result of cancer [4] , and close to 70% of all cancer deaths occur in low and middle-
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income countries. Approximately one in five people suffers from cancer before 75 years of age, while one in ten in this age range is predicted to die due to cancer [5] . The increasing rates of cancer indicate that there will be a 60% increase in cancer incidence by 2030 [6] . The causes of cancer can be broadly classified as external and internal factors. External factors include chemical exposure, radiation and viruses. For example, the risk of cancer is high among workers frequently exposed to ionizing radiation and toxic metals [7] . Internal factors include hormones, mutations and immune conditions, which may act chronologically to trigger or promote the process of carcinogenesis [8] . Radiation therapy, chemotherapy, surgery, immunotherapy, cancer vaccinations, photodynamic therapy, stem cell transformation, or a combination thereof is mainly used for
Nanomedicine (Lond.) (Epub ahead of print)
Muhammad Ovais*,1, Ali Talha Khalil1, Abida Raza2, Muhammad Adeeb Khan3, Irshad Ahmad4, Nazar Ul Islam5, Muthupandian Saravanan6, Muhammad Furqan Ubaid7, Muhammad Ali1 & Zabta Khan Shinwari1,8 $EPARTMENTOF"IOTECHNOLOGY 1UAID I !ZAM5NIVERSITY )SLAMABAD 0AKISTAN 2 .ATIONAL)NSTITUTEFOR,ASERS/PTRONICS 0AKISTAN!TOMIC%NERGY#OMMISSION )SLAMABAD 0AKISTAN 3 $EPARTMENTOF:OOLOGY 5NIVERSITYOF !ZAD*AMMU+ASHMIR -UZAFFARABAD 0AKISTAN 4 $EPARTMENTOF,IFESCIENCES +ING&AHD 5NIVERSITYOF0ETROLEUM-INERALS $HAHRAN 3AUDI!RABIA 5 $EPARTMENTOF0HARMACY 3ARHAD 5NIVERSITYOF3CIENCE)NFORMATION 4ECHNOLOGY 0ESHAWAR 0AKISTAN 6 $EPARTMENTOF-EDICAL-ICROBIOLOGY )MMUNOLOGY )NSTITUTEOF"IOMEDICAL 3CIENCES #OLLEGEOF(EALTH3CIENCES -EKELLE5NIVERSITY -EKELLE %THIOPIA 7 !ZAD*AMMU+ASHMIR-EDICAL #OLLEGE -UZAFFARABAD 0AKISTAN 8 0AKISTAN!CADEMYOF3CIENCES )SLAMABAD 0AKISTAN
!UTHORFORCORRESPONDENCE 4EL MOVAIS BSQAUEDUPK 1
part of
ISSN 1743-5889
Review
Ovais, Khalil, Raza et al.
cancer treatment, often accompanied by severe side effects. Such side effects include nonspecificity, limited bioavailability, toxicity, fast clearance and restriction in metastasis [9–11] . Numerous kinds of toxicities can result from the use of chemotherapeutic agents. For example, 5-fluorouracil is a commonly used chemotherapeutic entity associated with cardiotoxicity, myelotoxicity and the constriction of blood vessels [12] . Doxorubicin, another cancer preventive drug, is associated with renal toxicity, cardiotoxicity and myelotoxicity [13] . Similarly, bleomycin and cyclophosphamide are reported for cutaneous toxicity and bladder toxicity, respectively [14,15] . Keeping these facts in view, we are urged to explore novel strategies and develop potential agents for effective cancer treatment with negligible side effects. The interface of nanotechnology, plants & cancer Contrary to the established methodologies of cancer treatment, there is an emergent concern toward cheaper and more cost effective therapeutic agents using natural resources such as plants [9,16–18] . Medicinal plants have delivered new horizons for the treatment of cancer. They are not only a valuable resource for new chemical compounds through bioprospecting, but they also provide novel strategies for the treatment of cancer, like green synthesis of silver nanoparticles (AgNPs) (Figure 1) . In this respect, nanotechnology carries the potential to be applied at the molecular level to control the matter of apprehension. It is a dynamic field, involving biology, chemistry and physics of the nanoscale objects. Remarkable research in nanotechnology has opened up new avenues for drug delivery, treatment and diagnosis [19] . Nanotechnology coupled with metal nanoparticles has been successfully applied in various fields, especially biomedical sciences. In terms of treatment and diagnosis, nanoparticles are utilized due to their shape, size and unique optical and thermal characteristics [20,21] . These exceptional properties of metal nanoparticles, which are due to a ratio of particular size and elevated surface area to volume, make them ideal for many biological applications, including theranostics [22,23] . These distinctive structures are not shown by the macro-scale counter parts. Synthesis of nanoparticles can be carried out from different techniques broadly through physical and chemical methods. However, recent research indicates that biological methods have played a great role in the synthesis of metal nanoparticles [24,25] . Living organisms such as fungi and bacteria can be used to synthesize nanoparticles, but the synthesis platform involving plants provides an ecofriendly and adequate approach because it is devoid of the use of many expensive, toxic
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and harmful chemical compounds in media for growth [26,27] . Other advantages of plant-derived nanoparticles include rapid synthesis, increased stability and cost– effectiveness. In addition, nanoparticles of several sizes and shapes can be produced using plants as compared with other organisms [28] . Unlike bacteria and fungi that require relatively long incubation times for reduction of metal ions, the phytochemicals can do it rather quickly and eliminate the need of expensive and time consuming downstream processing. Green synthesis resources like fungi and bacteria trigger some biosafety issues, which are neutralized by using plants for green synthesis [18] . Therefore, plant-based platforms for green synthesis are the best candidates for synthesizing metal nanoparticles [29] . Over the last few years, there has been a paradigm shift in the strategies toward cancer treatment. With advancements in medicinal plants research and nanotechnology, there is a large increase in possible treatments of different types of cancer, benefitting patients economically [30,31] . This interface for manufacturing multifunctional, plant-derived nanoparticles has attracted many cancer treatment researchers and scientists [18,32–34] . These green-synthesized nanoparticles can overcome some of the footraces in conventional treatment and diagnostic therapies. The nanoparticles retain a site-specific and targeted activity that increases the efficacy of the drug, as the nanoparticles can evade immune responses and cross the impermeable membranes [35] , and therefore can be valuable for combating cancer. Metal nanoparticles possess surface plasmon resonance in UV-visible regions due to the coherent presence of free electrons in the conduction band, while dielectric constant, size and particle surroundings determine the band shift [36,37] . A unique feature of the metal nanoparticles is that absorbance of the wavelengths gives an idea about their shapes, sizes and interparticle properties [38,39] . Metal nanoparticles has been observed with enormous interest for developing alternative theranostic strategies of cancer treatment [40,41] . Engineered, biocompatible, functionalized and inert metal nanoparticles can be of significant interest in the coming years for cancer theranostics [20,42,43] . Monitoring and detection of tumors with labeled nanocrystals and targeted drug delivery with chemotherapeutic drugs have previously been established [20,44] . Plant extract-mediated green synthesis of AgNPs Metal nanoparticles are considered among the most efficient ones for biomedical applications due to their use as an imaging resource and their multifunctional theranostic abilities, such as their antibacterial, antitumor and drug carrier properties [45–47] . Colloidal silver
Nanomedicine (Lond.) (Epub ahead of print)
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Annona squamosa
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Solanum trilobatum
Dimocarpus longan Lour
Moringa oleifera
Olax scandens
Suaeda monoica
Plumeria alba
Melia dubia
Gymnema sylvestre
Melia azedarach
Oak
Vitex negundo L.
Sargassum vulgare
Rubus glaucus Benth
Rheum Emodi
Rosa indica
Podophyllum hexandrum Syzygium cumini
Catharanthusroseus
Azadirachta indica
Figure 1. Various medicinal plants exploited in the last decade for green synthesis of silver nanoparticles against cancer. Adapted with permission from [30,31] .
Heliotropium indicum
Cymodocea serrulata
Cucurbita maxima
Croton bonplandianum
Erythrina indica
Alternanthera sessilis Artemisia marschalliana
Citrullus colocynthis
Allium sativum
Acorus calamus
Achillea biebersteinii
Andrographis echioides Butea monosperma
Abutilon indicum
Abelmoschus esculentus
Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics
Review
10.2217/nnm-2016-0279
Review
Ovais, Khalil, Raza et al.
AgNPs
Sol-gel process
Sputtering
up Bo ttom
Vapour deposition
Bulk
Clusters
Atomic/molecular condensation
Chemical etching
Nanoparticle synthesis Top
Spray pyrolysis
n
dow
Chemical/electrochemical deposition Aerosol process
Thermal/laser ablation Mechanical/ball missling Explosion process
Bioreduction Powder Atoms
AgNPs
Figure 2. Different physical, chemical and biological methods for production of silver nanoparticles. AgNP: Silver nanoparticle.
is considered a potent anticancer and antimicrobial agent; therefore, significant research is focused only on AgNPs [48] . There are various chemical, physical and biological ways to synthesize AgNPs, including Bottom Up and Top Down strategies (Figure 2) . The chemical means of synthesis include chemical compounds to reduce Ag+ to AgNPs; however, the chemical methods are often undesirable because of low biocompatibility [49] . Green synthesis, also called biogenic synthesis, is considered an alternative approach for synthesizing the AgNPs and has given rise to a novel field: ‘Phytonanotechnology’, which deals with green synthesis of metal nanoparticles via exploitation of plant resources and further comprises its optimization and applications. The shape and size of the AgNPs is affected by the solvent type, stabilization and reduction [50] . The process of synthesis starts after incubation of the plant extracts with silver salts (silver nitrate is mostly used). The synthesis of noble AgNPs is a two-step process that first comprises the reduction of Ag+ ions to Ag°, followed by the agglomeration and stabilization that lead to the
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formation of oligomeric clusters of colloidal AgNPs [51] . The process of reduction takes place in the presence of biological catalysts, as graphically illustrated in Figure 3. Optimized conditions for biogenic AgNPs synthesis The reaction parameters play a critical role in optimizing the yield, size and stability of biogenic AgNPs. Different parameters can be optimized for the synthesis, such as concentration of the plant material, concentration of silver salt, pH and temperature at which the reaction is carried out, and incubation time for the reaction [52] . These factors have a prodigious impact on the size, shape and other properties of AgNPs. The first evidence of AgNPs synthesis is observed when the reaction solution containing Ag-salt and plant material turns from colorless to dark brown. Synthesis of AgNPs is reported in different ranges of pH (i.e., 2–14 [53]); however, pH 7 is considered optimal for its synthesis [54] . AgNPs can be produced at dif-
Nanomedicine (Lond.) (Epub ahead of print)
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Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics
Review
Ag0
Cancer theranostics Ag0
Ag0
Ag0 Ag0
Ag Ag0 Ag0 Ag0 0
Phytochemicals coated AgNPs
Terpenoids Cancer therapy
Stabilization Cancer nanomedicine
0 0 Ag0 Ag Ag 0 0 Ag Ag0 Ag 0 Ag
Growth Plant extracts
AgNO3
Ag+2 Ag+2 Ag+2 +2 Ag
H2O
Ag0 Ag0 Ag0
Reduction
Phenolics
Phytochemicals
Cancer diagnosis
Flavinoids Alkaloids Amino acids Vitamins
Polysaccharides
AgNO3 solution Figure 3. Plant-mediated mechanism of biogenic silver nanoparticles production: a step forward for cancer nanomedicine. AgNP: Silver nanoparticle.
ferent temperatures (40°C); however, room temperature (25°C) has been found to be optimal for the synthesis of spherical and small AgNPs that have surface plasmon resonance at low wavelengths [16] . Such AgNPs tend to show relatively good biological properties [55] . Mostly sharp peaks are associated with low temperature-mediated synthesis, which produces uniformly sized AgNPs, while broad peaks are associated with higher temperature-mediated synthesis [56] . However, depending upon different reaction conditions and plant parts used, the nature of peaks may change [55] . A current review article clearly elaborates on the role of plant terpenoids in the synthesis of biogenic AgNPs, with special focus on the Fourier Transformed Infrared Spectroscopy (FTIR) in elucidation of main functional groups in terpenoids for AgNPs capping [51] . Concentration of silver salt in the reaction is kept in the 0.25–10 mM range, as concentration above 10 mM can cause accumulation of silver and unclear surfaces. With the increase in salt concentration, the surface plasmon bands move to a higher range, which is an indication of agglomeration. The
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incubation time for the reaction also plays a critical role in the yield of AgNPs [57,58] . Once the synthesis of AgNPs has taken place, we further have to centrifuge the solution on 10,000–15,000 RPM for 10 minutes. The supernatant is discarded while the pellet is rediluted with deionized H2O, followed by centrifugation in similar conditions (the washing step is repeated three times) [16] . Further characterization needs to be carried out for proper identification of attached functional groups and size elucidation of biogenic AgNPs. Frequently used techniques for the characterization of AgNPs include x-ray diffraction studies in order to differentiate between the amorphous and crystalline natures of AgNPs; scanning and transmission electron microscopy for detailed information regarding morphology and size; FTIR to help in identifying functional groups attached to nanoparticles’ surfaces; and Zetasizers to give information about ζ-potential (i.e., stability of AgNPs) and size. For these entire characterization techniques, nanoparticle samples should be prepared according to the type of characterization technique performed.
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10.2217/nnm-2016-0279
10.2217/nnm-2016-0279 2
Nanomedicine (Lond.) (Epub ahead of print)
XRD
SEM/TEM
Other techniques
Characterization
FTIR
3
Salt concentration
5
Pl an ss
1
t ti ue s
Fruit Roots
Cell SNPs
Clinical trials
Clinical trials
Applications in cancer theranostics
Proteins Alkaloids Cellulose Chrophyll Polysaccharides Flavinoids Terpenoids Phenolics Amino acids Vitamins Other metabolities
Cell labelling
Diagnosis
Temperature
Bioimaging
Extract concentration
Optimized conditions
PH
Leaf
Peel
Brain cancer Skin cancer Breast cancer Bladder cancer Colorectal cancer Prostate cancer
Therapy
Stem
Flowers
Figure 4. Full scheme of biogenic silver nanoparticles synthesis, optimization, characterization and potential application as cancer theranostics agent. In Step 1 the biological material in the form of phytochemicals from various sources is extracted, followed by its mixing in Step 2 with AgNO3. Synthesis and optimization is done in Step 3. In Step 4 characterization is done to elucidate the properties of biogenic AgNPs and in Step 5 application of these biogenic nanoparticles is performed in cancer theranostics. AgNP: Silver nanoparticle.
UV
4
Biological synthesis of silver nanoparticles
AgNO3 solution
Ag+2 ions
Review Ovais, Khalil, Raza et al.
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Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics
Review
Biogenic
AgNO3
AgNPs
Cancer cell dies Anticancer activity 4-in-1 systems Olax scandens
E-coli
Red fluorescence Diagnostic/bio-imaging
Antibacterial Biocompatible/nontoxic
Figure 5. Biomedical applications (diagnostic, anticancer antibacterial applications) of green synthesized silver nanoparticles using Olax scandens leaf extract. AgNP: Silver nanoparticle. Adapted with permission from [45] .
Biogenic AgNPs: advancements in cancer theranostics In recent years, nanoparticles have been extensively researched for the purpose of therapy and diagnosis of cancer. Biogenic AgNPs are functionalized with phytochemical coating, rendering them more biologically active as compared with chemically synthesized AgNPs. Besides application of biogenic AgNPs in cancer theranostics, many groups have reported diverse applications of biogenic AgNPs, such as antimicrobial, antileshmanial, wound healing, antiviral, antitubercular and antidiabetic properties, and many more [59–66] . Figure 4 shows in detail the full scheme of biogenic AgNP synthesis, optimization, characterization and potential application as a cancer theranostics agent. Although many researchers across the globe are working in phytonanotechnology, S Mukherjee et al. [45] have introduced for the first time a 4-in-1 multifunctional system. They have synthesized biogenic AgNPs from leaf extract of Olax scandens, which shows anticancer and antibacterial activities. Moreover, these biogenic AgNPs were biocompatible to normal cell lines and possess self-fluorescence ability
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(a diagnostic approach) as sketched in Figure 5. Many studies have demonstrated anticancer activity of plant extract-mediated green-synthesized AgNPs on a variety of cancer cell lines, such as Jurkat cell line (human T-cell lymphoma), COLO 205 (colon carcinoma), MCF-7 (human breast cancer), HEPG2 (human liver cancer), PC3 (human prostate cancer), AGS (human gastric carcinoma), SiHa (cervical cancer), HCT-116, HCT-15 (human colon adenocarcinoma), Hep-G2 (liver carcinoma), Caco-2 (intestinal adenocarcinoma), HeLa (cervical cancer), Hek-293 (kidney cancer), H1299, A549 (lung cancer), PA1 (ovarian cancer), HL-60 (human promyelocytic leukemia cells), B16 (mouse melanoma cell line), A431 (epidermoid carcinoma), VCaP (prostate cancer) and BxPC-3 (pancreas cancer) [45,67–103] . Table 1 extensively elaborates on the anticancer results and optimized conditions for biogenic AgNP synthesis from studies conducted in the previous decade. Biogenic AgNPs & cancer therapy: a mechanistic approach The proposed mechanism for anticancer activity
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10.2217/nnm-2016-0279
Nanomedicine (Lond.) (Epub ahead of print)
Acorus calamus
Allium sativum
Alternanthera sessilis
Alternanthera sessilis
Andrographis echioides
Artemisia marschalliana
Azadirachta indica
Azadirachta indica
Butea monosperma
Citrullus colocynthis
Nayak et al. (2015)
Pandian et al. (2015)
Lalitha et al. (2015)
Firdhouse et al. (2013)
Elangovan et al. (2015)
Salehi et al. (2016)
Mishra et al. (2012)
Mittal et al. (2016)
Patra et al. (2015)
Shawkey et al. (2013)
12 59
20 μg/ml 78.58 μg/ ml
2–18
≤4.25 μg/ ml Dose 30 (μg/ ml)on all cell lines
>30, 2.4, 17.2, >30 (μg/ml)
>30, >30, 10.02, >30 (μg/ml)
16.57
7.39
13.37
Spherical
Spherical
Spherical
Spherical
Spherical
Triangular, hexagonal
Spherical
Cubic, UV–Vis, FTIR, SEM, pentagonal, AFM, XRD, EDX hexagonal
68.06
31.5 μg/ml
UV–Vis, TEM
UV–Vis, TEM
UV–Vis, TEM
UV–Vis, FTIR, TEM, XRD, EDX, XPS
UV–Vis, TEM, EDX
UV–Vis, TEM, XRD
UV–Vis, FTIR, SEM, TEM, XRD, EDX
UV–Vis, FTIR, SEM, XRD
Spherical
6.85 μg/ml 30–50
UV–Vis, TEM
UV–Vis, FTIR, SEM
UV–Vis, DLS, SEM, XRD, FTIR
UV–Vis, DLS, TEM, FTIR
UV–Vis, DLS, TEM, SEM, EDX, XRD, FTIR
UV–Vis, DLS, TEM, XRD, FTIR
Spherical
Spherical
Spherical, cuboidal
Spherical, pentagonal
Spherical
Spherical
Techniques used‡
Characterization Shape
3.04 μg/ml 10–30
100– 800
5–25
4 μg/ml
31.25 ng/ ml (LD50 )
∼6.7
16.15 μg/ ml
Size (nm)
B16F10, MCF-7, Dose 20–80 HNGC2 & A549 dependent
HeLa, Hek-293 and MCF-7
SiHa
AGS
MCF-7
PC3
MCF-7
HEPG2
Leaf
Leaf
Leaf
Leaf
Aerial part
Leaf
Leaf
Aerial parts
Whole plant
Rhizome A431
MCF-7
COLO 205
Jurkat
Cancer cell line† IC50value
5
5
5
0.1
1
1
0.01
1
3
3
1
1M
5
1
1
Neutral
Neutral
Neutral
Neutral
Neutral
8
Neutral
Neutral
Neutral
Neutral
Neutral
2–10
Neutral
Neutral
Neutral
3h
3h
27 h
Incubation time
Room
Room
Room
Room
Room
Room
Room
Room
Room
Room
Room
24 h
24 h
24 h
2h
6h
–
5 min
12 h
6h
6h
48 h
20–100 5–60 min
40
Room
Room
Temp (°C)
Optimal variables AgNO3 pH (mM)
[98]
[91]
[86]
[85]
[95]
[72]
[67]
[82]
[90]
[88]
[69]
[84]
[87]
Ref.
#ANCERCELLLINES!%PIDERMOIDCARCINOMA!,UNGCANCER!'3(UMANGASTRICCARCINOMA"-OUSEMELANOMACELLLINE"X0# 0ANCREASCANCER#ACO )NTESTINALADENOCARCINOMA#/,/#OLON CARCINOMA(#4 (#4 (UMANCOLONADENOCARCINOMA(E,A#ERVICALCANCER(EK +IDNEYCANCER(EP ',IVERCARCINOMA(%0'(UMANLIVERCANCER( (, (UMANPROMYELOCYTICLEUKEMIA CELLS*URKATCELLLINE(UMAN4 CELLLYMPHOMA-#& (UMANBREASTCANCER0#(UMANPROSTATECANCER3I(A#ERVICALCANCER0!/VARIANCANCER6#A00ROSTATECANCER‡Techniques used:!&-!TOMICFORCE MICROSCOPE$,3$YNAMICLIGHTSCATTERING%$8%NERGY DISPERSIVEX RAY&4)2&OURIERTRANSFORMINFRARED)#0 /%3)NDUCTIVELYCOUPLEDPLASMAOPTICALEMISSIONSPECTROMETER3%-3CANNINGELECTRONMICROSCOPY 4%-4RANSMISSIONELECTRONMICROSCOPY4'!4HERMOGRAVIMETRICANALYZER56n6IS56nVISIBLEABSORPTIONSPECTROSCOPY82$8 RAYDIFFRACTION8038 RAYPHOTOELECTRONSPECTROSCOPYFCC:&ACE CENTERED CUBIC
†
Achillea biebersteinii
Baharara et al. (2015)
Flower
Leaf
Abutilon indicum
Mata et al. (2015)
Part used
Pulp
Plant
Mollick et al. Abelmoschus (2015) esculentus
Study (year)
Table 1. List of studies exploiting plant extracts for green synthesis of silver nanoparticles as therapeutics and diagnostics agents for cancer.
Review Ovais, Khalil, Raza et al.
future science group
future science group
petal
Cucurbita maxima
Cymodocea serrulata
Cymodocea serrulata
Dimocarpus longan
Erythrina indica
Nayak et al. (2015)
Palaniappan et al. (2015)
Chanthini et al. (2015)
He et al. (2016)
Sre et al. (2015)
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Leaf
Melia dubia
Moringa oleifera
Olax scandens
Kathiravan et al. (2014)
Nayak et al. (2015)
Bhadra et al. (2014)
Fruit
Leaf MCF-7
A549, B16, MCF-7
A431
MCF-7
HeLa
HeLa
HT29
MCF-7, Hep-G2
H1299, VCaP, BxPC-3
HeLa
A549
A431
PA-1, A549
Hep -2
HCT-116, MCF7, Hep-G2, Caco-2 31 32 76 29.28
3.42 μg/ml 7.5 μg/ml 82.39 μg/ ml 100 μg/ml (LD50 )
80– 120 78 7.3 94
20 μg/ml 300 μg/ml (LD50 ) 31.2 μg/ml 83.57 μg/ ml
67 μg/ml
46
Dose 30–60 dependent
Spherical
-
85 μg/ml
Spherical
Spherical
Spherical, cuboidal
Irregular
Cubical, spherical
Spherical
20–118 Spherical
Spherical
Spherical
Spherical
Spherical, cuboidal
Spherical
Spherical
Spherical
UV–Vis, DLS, SEM, FTIR
UV–Vis, DLS, TEM, XRD, FTIR, ICP-OES
UV–Vis, DLS, SEM, XRD, FTIR
UV–Vis, SEM, XRD, FTIR
UV–Vis, DLS, SEM, XRD, FTIR
UV–Vis, DLS, SEM, XRD, FTIR
UV–Vis, EDX, SEM, XRD, FTIR
UV–Vis, DLS, EDX, SEM, XRD, FTIR
TEM, SEM
UV–Vis, DLS, EDX, SEM, XRD, FTIR
UV–Vis, DLS, TEM, SEM, XRD, FTIR
UV–Vis, DLS, SEM, XRD, FTIR
UV–Vis, TEM, SEM, XRD
AFM, FTIR
UV–Vis, TEM
Techniques used‡
Characterization Shape
23.89, 13.86 (% viability)
5.33, 87.33, 8-22 38.9 μg/ml
107.7 (GI50 ) 17-29
19.26
Size (nm) 21.2, >30, 22.4, >30 (μg/ml)
Cancer cell line† IC50value
1
100
1M
10
1
1
1
1
2
1
1
1M
1
1
5
Neutral
Neutral
2–10
Neutral
Neutral
Neutral
Neutral
Neutral
Neutral
Neutral
Neutral
2-10
Neutral
Neutral
Neutral
1h
24 h
24 h
Incubation time
15 m
10 m
2h
24 h
Overnight
2h
2h
1h
Room
Room
6h
2h
20–100 5–60 min
Room
30-95
Room
Room
Room
80
Room
4, room, 60
20–100 5–60 min
60
Room
Room
Temp (°C)
Optimal variables AgNO3 pH (mM)
[94]
[45]
[88]
[78]
[100]
[149]
[68]
[99]
[74]
[70]
[89]
[88]
[80]
[96]
Ref.
†
#ANCERCELLLINES!%PIDERMOIDCARCINOMA!,UNGCANCER!'3(UMANGASTRICCARCINOMA"-OUSEMELANOMACELLLINE"X0# 0ANCREASCANCER#ACO )NTESTINALADENOCARCINOMA#/,/#OLON CARCINOMA(#4 (#4 (UMANCOLONADENOCARCINOMA(E,A#ERVICALCANCER(EK +IDNEYCANCER(EP ',IVERCARCINOMA(%0'(UMANLIVERCANCER( (, (UMANPROMYELOCYTICLEUKEMIA CELLS*URKATCELLLINE(UMAN4 CELLLYMPHOMA-#& (UMANBREASTCANCER0#(UMANPROSTATECANCER3I(A#ERVICALCANCER0!/VARIANCANCER6#A00ROSTATECANCER‡Techniques used:!&-!TOMICFORCE MICROSCOPE$,3$YNAMICLIGHTSCATTERING%$8%NERGY DISPERSIVEX RAY&4)2&OURIERTRANSFORMINFRARED)#0 /%3)NDUCTIVELYCOUPLEDPLASMAOPTICALEMISSIONSPECTROMETER3%-3CANNINGELECTRONMICROSCOPY 4%-4RANSMISSIONELECTRONMICROSCOPY4'!4HERMOGRAVIMETRICANALYZER56n6IS56nVISIBLEABSORPTIONSPECTROSCOPY82$8 RAYDIFFRACTION8038 RAYPHOTOELECTRONSPECTROSCOPYFCC:&ACE CENTERED CUBIC
Piper longum
Melia azedarach Leaf
Sukirtha et al. (2012)
Reddy et al. (2014)
Whole Plant
Heliotropium indicum
Vijistella Bai (2014)
leaf
Leaf
Arunachalam Gymnema et al. (2015) sylvestre
Root
peel
Whole plant
Leaf
Leaf
Khanra et al. Croton (2016) bonplandianum
Callus
Citrullus colocynthis
Satyavani et al. (2011)
Part used
Fruit
Plant
Shawkey et al. (2013) (cont.)
Study (year)
Table 1. List of studies exploiting plant extracts for green synthesis of silver nanoparticles as therapeutics and diagnostics agents for cancer (cont.).
Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics
Review
10.2217/nnm-2016-0279
10.2217/nnm-2016-0279
Solanum trilobatum
Suaeda monoica Leaf
Syzygium cumini Flower
Ramar et al. (2015)
Satyavani et al. (2012)
Mittal et al. (2016)
Nanomedicine (Lond.) (Epub ahead of print)
HCT-15
Hep-2, MF7, HT29
HeLa, Hek-293, MCF-7
Hep-2
MCF-7
MCF-7
PA-1, A549
HL60, HeLa
Hep-G2
HCT 15
A549
MCF-7
MCF-7
HeLa
COLO 205
20 μg/ml
22
12.5, 37, 49 56 μg/ml
Dose