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Review
Biological Synthesis of
Nanoparticles from Plants and Microorganisms Priyanka Priyan ka Sin Singh, gh,1 Y u-Ji u -Jin n Ki Kim, m,1,2,* Da Dabi bin ng Zh Zhan ang, g,2 and Deok-C Deo k-Chun hun Yan Yang g1,* Nanotechnology has become one of the most prom promising ising technologies applied in alll ar al area eas s of science. Metal nanoparticles produced by nanotechnology have receive rec eived d glo global bal attention due to their extensive applications in the biomedical and phy physio siochem chemical ical elds. Recently, synthesizing met metal al nan nanopa oparti rticle cles s using microorgan micro organisms isms and plants has been extensively studied and has been recogniz ized ed as a green and ef ci cien entt way for further exploiting mic microo roorga rganis nisms ms as convenient conve nient nanof nanofactori actories. es. Here, we explore and detail the potential uses of variou var ious s bio biolog logica icall sources for nanoparticle synthesis and the application of those nanop nanoparticl articles. es. Furthermore, we highlight recent milestones achieved for the th e bi biog ogen enic ic synthesis of nanoparticles by controlling critical parameters, inc nclu ludi ding ng th the e choice of biological source, incubation period, pH, and temperature.
Meta Metall na nano nopa part rtic icle les s pr prod oduc uced ed usin using g micr microo oorg rgan anis isms ms an and d pl plan antt extr extrac acts ts are are stab stable le an and d can can be mono monodis dispe perse rsed d by cont contro rolllling ing synt synthe heti tic c pa para rame mete ters, rs, such such as pH pH,, temp temper erat ature ure,, in incu cuba bati tion on per period iod,, and mixing n g ratio. ratio.
The biological synthesis of nanoparticles cles is increa increasin singlyregard glyregarded ed as a rapid, rapid, ecofr iendly, and easil y scaled-up technology.
Trends
Recently, biological Recently, biological nanop nanoparticl articles es were foun found d to be more more ph phar arma maco colo logi gica callllyy act active ive tha than n phy physic sicoch ochemi emical calllyy syn synthe the-sized nanop nanoparticle articles. s.
Nanopa Nan oparti rticle cles s and their Applications
Nanotechnology (see Glossary ) has become one of the most important technologies in all areas of science. It relies on the synthesis and modulation of nanoparticles, whic which h requires signicant modications of the properties of metals [1] [1].. Nanomaterials have in fact been used unknowingly for thousands of years; for example, gold nanoparticles that were used to stain drinking glasses also cured certain diseases. Scientists have been progressively able to observe
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the shape- and size-dependent physiochemical properties of nanoparticles by using advanced techniques. Recently, the diverse applications of metal nanoparticles have been explored in biomedical, agricultural, environmental, and physiochemical areas (Figure 1 ) [1–5] 5].. For For instance, gold nanoparticles have been applied for the specic delivery of drugs, such as paclitaxel, methotrexate, and doxorubicin [2] [2].. Gold nanoparticles have been also used for tumor detection, angiogenesis, genetic disease and genetic disorder diagnosis, photoimaging, and photothermal therapy. Iron oxide nanoparticles have been applied for cancer therapy, hyperthermia, drug delivery, tissue repair, cell labeling, targeting and immunoassays, detoxication of biological uids, magnetic resonance imaging, and magnetically responsive drug delivery therapy [6– 8].. Silver nanoparticles have been used for many antimicrobial purposes, as well as in anticancer, 8] [9].. Due to their biocompatible, nontoxic, anti-inammatory, and wound treatment applications [9] self-cleansing, skin-compatible, antimicrobial, and dermatological behaviors, zinc and titanium nanoparticles have been used in biomedical, cosmetic, ultraviolet (UV)-blocking agents, and various cutting-edge processing applications [10,11] [10,11].. Copper and palladium nanoparticles have been applied in batteries, polymers, plastics plasmonic wave guides, and optical limiting devices [12,13].. Moreover, they were found to be antimicrobial in nature against many pathogenic [12,13] microorganisms. Additionally, metal nanoparticles have been used in the spatial analysis of various biomolecules, including several metabolites, peptides, nucleic acids, lipids, fatty acids,
Among the various biological nanoparticl ticles es,, th thos ose e pr prod oduc uced ed by medi medici cina nall pl plan ants ts ha have ve be been en foun found d to be th the e most most pharmacologi pharma cologic cally ally active active,, possibly bly due to th the e atta attach chme ment nt of seve severa rall ph phar arma ma-cologic cally ally active residues. residues.
http://dx.doi.org/10.1016/j.tibtech.2016.02.006
Depart Dep artme ment nt of Ori Orient ental al Medic Medicine ine Bio Biotec techno hnolog logy, y, Col Colleg lege e of Lif Life e Scienc Science, e, Kyu Kyung ng Hee Uni Univer versi sity ty,, Yongin Yongin 446-70 446-701, 1, Kor Korea ea 2 Joint Internati International onal Rese Research arch Labora Laborator tory y of Metabo Metaboli lic c & Developm Deve lopmental ental Scien Sciences, ces, Shanghai Shanghai Jiao Jiao Tong Tong Uni Univer versi sity ty–Univ Universi ersity ty of Adelaide Joint Centre for Agriculture and and Heal Health th,, Stat State e Ke Key y Labo Labora rato tory ry of Hy Hybr brid id Ri Rice ce,, Scho School ol of Life Life Scie Scienc nces es and Bio Biotec techno hnolog logy, y, Sha Shangh nghai ai Jia Jiao o Tong Tong Uni Univer versi sity, ty, Sha Shangh nghai, ai, Chi China na
1
*Correspondence:
[email protected] (Y. (Y.-J. -J. Kim Kim)) and
[email protected] (D.-C. Yang).
glycosphingolipids, and drug molecules, to visualize these molecules with higher sensitivity and spatial resolution [14] [14]..
In addition, the unique properties of nanoparticles make them well suited for designing electro[15].. For example, nanosensors have been developed for the chemical sensors and biosensors [15]
detection of algal toxins, mycobacteria, and mercury present in drinking water [16] [16].. Resear Researchers chers also developed nanosensors by utilizing nanomaterials for hormonal regulation and for detecting crop pests, viruses, soil nutrient levels, and stress factors. For instance, nanosensors for sensing [17].. auxin and oxygen distribution have been developed [17]
To date, due to the physiochemical properties and many applications of nanoparticles, the scientic community has dedicated extensive efforts to develop suitable synthetic techniques for producing nanoparticles. However, various physiochemical approaches for the synthesis of metal nanoparticles are limited by the environmental pollution caused by heavy metals. Thus, synthesizing nanoparticles by biological means, which has the advantages of nontoxicity, reproducibility in production, easy scaling-up, and well-dened morphology, has become a new trend in nanoparticle production. In particular, microorganisms and plants have been demonstrated as new resources with considerable potential for synthesizing nanoparticles. To date, several microorganisms, including bacteria, fungi, and yeast, as well as plants, have been explored for the synthesis of metal nanoparticles. While the synthesis of nanoparticles has been extensively reviewed elsewhere [5,18–20] 20],, he here re we provide an update on recent advances in the synthesis of biological nanoparticles, and describe prospects for their future development and applications.
Nanoparticle Synthesis Using Microorganisms
Microorganisms have been shown to be important nanofactories that hold immense potential as ecofriendly and cost-effective tools, avoiding toxic, harsh chemicals and the high energy demand required for physiochemical synthesis. Microorganisms have the ability to accumulate and detoxify heavy metals due to various reductase enzymes, which are able to reduce metal salts to metal nanoparticles with a narrow size distribution and, therefore, less polydispersity. The mechanism and experimental methods of synthesizing nanoparticles in microorganisms is described in Box 1. Over the past few years, microorganisms, including bacteria (such as actinomycetes), fungi, and yeasts, have been studied extra- and intracellularly for the synthesis of metal nanoparticles ( Table Table 1 ). An array of biological protocols for nanoparticle synthesis has
compatibility Biocompatibility: the compatibility and non noninju injuriou rious s eff effect ects s of met metal al nan nanopa oparti rticle cles s wit within hin the human human bod bodyy or hea health lthyy living n g cellls. s. Biological Biolo gical nanofacto nanofactories: ries: biological
sou source rces s cap capabl able e of syn synthe thesiz sizing ing metal nano nanopartic particles, les, inclu including ding microorganis microo rganisms ms and plants plants.. Biological Biolo gical nanopartic nanoparticles: les: nanoparticl nanop articles es obtain ntend tend form biolog biologica icall sou source rces, s, such such as micoro micorogan ganism isms s and pla plant nt extrac extracts. ts. Biological Biolo gical synthesis: synthesis: synthesis using using nat natura urall source sources, s, avoidin avoiding g any toxic toxic che chemic micals als and haz hazard ardous ous byproduc products, ts, usu usuall allyy wit with h low lower er energy energy consumption. Magnetical Magn etically ly responsive responsive drug deliv liver eryy of he heav avyy dr drug ugs s by delivery: de magnet mag netic ic nan nanopa opartic rticles les und under er the inue uenc nce e of an exte externa rnall magn magnet etic ic eld. biological ical synthe synthesis sis Mycosynthesis: biolog
Glossary
of metal metal nan nanopa opartic rticles les from from fun fungi. gi. Nanoparticles: sma smallll par partic ticles les wit with h all thr three ee dimens dimension ions s mea measur suring ing 20
Luminescence, photocatalytic and antioxidant antioxidant
[58]
Citrus Citru s medica medica
Fruit
Copper
–
20
Antimicrobial
[59]
Orange an and pi pineapple
Fruits
Silver
Spherical
10–300
–
[60]
Lawsonia Laws onia inermis
Leaves
Iron
Hexagonal
21
Antibacterial
[61]
Gardenia Garde nia jasmin jasminoides oides
Leaves
Iron
Rock like appearance
32
Antibacterial
[61]
have signicant roles in metal salt reduction and, furthermore, act as capping and stabilizing [62].. For instance, El-Kassas et al. showed that the agents for synthesized nanoparticles [62] hydroxyl functional group from polyphenols and the carbonyl group from proteins of Corallina of cinalis extract could assist in forming and stabilizing gold nanoparticles [63] [63].. Philip et al. cinalis showed the synthesis and stabilization of silver and gold nanoparticles by biomolecule attachment in Murraya koenigii leaf extract [64] [64].. Re Repo port rts s also suggest that different mechanisms for synthesizing nanoparticles exist in different plant species [18] [18].. For instance, specic
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components, such as emodin, a purgative resin with quinone compounds that is present in xerophytes plants (plants adapted to survive in deserts or environments with little water) are responsible for silver nanoparticle synthesis; cyperoquinone, dietchequinone, and remirin in mesophytic plants (terrestrial plants adapted to neither a particularly dry nor particularly wet environment) are useful for metal nanoparticle synthesis. Eugenol, the main terpenoid of
Cinnamomum zeylanisum zeylanisum,, was found to have a principal role in the synthesis of gold and silver [19].. Nota Notabl bly, y, dicot plants contain many secondary metabolites that may be nanoparticles [19] suitable for nanoparticle synthesis ( Table Table 2 ).
Critical Parameters for the Biological Synthesis of Nanoparticles
Despite Despi te sev severa erall adv advant antage ages s of a bio biolog logica icall syn synth thesi esis s app approa roach ch for nan nanopa oparti rticle cles, s, th the e polydispe dispersi rsity ty of the nano nanoparti particles cles formed formed rem remain ains s a challenge. Therefor Therefore, e, many recent studies have attempted to rat ration ionall allyy est establ ablish ish a st stab able le syst system em for for pr prod oduc ucin ing g nanoparticles with homogenous homog enous size and morph morphology ology ( Tables Tables 1 and 2 ). Con Contro troll of the shape and size of me meta tall nanopa nan oparti rticle cles s has bee been n shown by either const constraini rainin ng g their env enviro ironme nment ntal al gro growth wth or altering the func functiona tionall molecu molecules les [26,65] [26,65].. For ins ta tance, 20–nm monod monodisper ispersed sed and biocompatible gold nan nanop opart articl icles es wer were e syn synth thesi esized zed usi using ng Ganoderma spp. by im impr prov ovin ing g th the e reaction conditions, including pH, tempe temperatu rature, re, incubation period, sal saltt con concen centra tratio tion, n, aerati aeration on,, red redox ox [66].. Growing mic microo roorga rgani nisms sms at th the e maxi maximu mum m conditions, mixi mixing ng ra rati tio, o, and and irra irradi diat atio ion n [66] possible poss ible temp temperatu erature re for opt optima imall gro growth wth is recom recommende mended d for the the synt synthe hesi sis s of nanoparticles using micro microorgan organisms, isms, becau because, se, at high igh temperatures, th the e en enzy zyme me responsible for for nan anoopartic par ticle le syn synthe thesis sis is more active [67]. [67]. pH is also one of the most inuential factors and different nano nanoparti partic cles les can be syn synthe thesiz sized ed at di diffe fferen rentt pH val values ues.. For ins instan tance, ce, Gur Guruna unatha than n et al. showed that mos mostt silver silver nan nanopa oparti rticle cles s we were re synt synth hesiz esized ed at pH 10 in Esch Escherich erichia ia coli [67] [67].. Among fungi, alkali alkaline ne pH (for Isari Isaria a fumos fumosorose orosea a [68] ), ), pH 6.0 (for Peni Penicilliu cillium m fellu fellutanu tanum m ), and ac acid idic ic pH (for Fusar Fusarium ium acumi acuminatu natum m ) were show shown n to be optimal for nanop nanoparti article cle [67] ), synthesis synt hesis.. For plants, pH cha change nges s lea lead d to cha change nges s in the ch char arge ge of natur natural al phyt phytochemi ochemicals, cals, which furt further her affec affects ts their binding ability and the reduction of metal ions duri during ng nanop nanoparti article cle synthe syn thesis sis.. This This in turn may aff affect ect the morph morphology ology and and yiel yield d of nan nanop opart articl icles. es. For instan instance, ce, in Avena sativa extr extrac act, t, at pH 3.0 and 4.0, nume numerous rous smal small-size l-sized d gold gold nan nanopa oparti rticle cles s were formed, whe wherea reas, s, at pH 2.0, nanop nanopartic article le aggre aggregatio gation n was observed. Therefor Therefore, e, it has been een suggested that, at aci acidi dic c pH val values ues,, nan nanopa oparti rticle cle agg aggreg regati ation on is dominant over th the e pro proces cess s of reduction.
This effect may be related to the fact that a larger number of functional groups that bind and nucleate metal ions become accessible at pH 3.0 and 4.0 compared with pH 2.0. At pH 2.0, the most accessible metal ions are involved in a smaller number of nucleation events, which leads to [69].. By contrast, it was demonstrated using extracts from pears the agglomeration of the metal [69] that hexagonal and triangular gold nanoparticles are formed at alkaline pH values, whereas nanoparticles do not form at acidic pHs [70] [70].. In the case of silver nanoparticle synthesis from the tuber powder of Curcuma longa longa,, at alkaline pHs, extracts may contain more negatively charged functional groups, which are capable of ef ciently binding and reducing silver ions and, thus, [69].. Another example of size- and shape-controlled more nanoparticles were synthesized [69] al.,, who demonstrated the size-controlled green biological synthesis was shown by Kora et al. synthesis of silver nanoparticles of 5.7 0.2 nm by Anogeissus latifolia [55] [55].. Triangular gold nanoparticles were synthesized by Cymbopogon exuosus exuosus extract [71] [71].. Similarly, other conditions, such as duration time, salt concentrations, and localizations for nanoparticles synthesis [5].. depend on species and extracts (Figure 2 ) [5]
Advantage of Biological Nanoparticles
The biocompatibility of nanoparticles, such as reduced metal cytotoxicity, is required for nanoparticles with biomedical applications. Compared with physicochemically derived
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Biological synthesis Microorganism or plant extract
Metal salt concentraon
Producon of heterogeneous NPs with low yield
Processing parameters:
n o a z i m p O
1. Incubaon period 2. Mixing rao 3. Temperature 4. pH 5. Aeraon
Stable producon of homogenous and capped NPs with high yield Metal salts Metal nanoparcles (NPs)
Modify processing parameters
Square
Triangular Hexagonal
Spherical
Rod
Controlled shape and morphology of NPs
Figure 2. Parameters for Producing Monodispersed, Stable, and High-Yield Biological Nanoparticles. I t is
wide widely ly acce accept pted ed that that extr extrac acts ts of mi micr croo oorg rgan anis isms ms and and pl plan ants ts can can be us used ed to sy synt nthe hesi size ze meta metall na nano nopa parti rticles c les.. Ho Howe weve ver, r, contro controllin lling g parame parameter ters, s, such such as salt concen concentra tration tion,, mixing mixing ratio ratio of biolog biologica icall extrac extractt and metal metal salt, salt, pH value, value, tem temper peratu ature, re, incu incuba bati tion on tim time, e, and and aera aerati tion on,, still still requ require ires s op opti timiz mizat atio ion n for for pr prod oduc ucin ing g ho homo moge geno nous us na nano nopa parti rticles c les of a simi simila larr size size and and sha shape. pe. Biolog Biologica icall synthe synthesis sis can als also o provid provide e an additio additional nal cap cappin ping g lay layer er on syn synthe thesize sized d nanopa nanopartic rticles les wit with h the att attach achmen mentt of seve severa rall bi biol olog ogic ical ally ly acti active ve grou groups ps,, whic which h can can enha enhanc nce e the the ef cac cacyy of biolog biologica icall nan nanopa opartic rticles les..
nanoparticles, nanoparticles obtained from biogenic routes are free from toxic contamination of by-products that become attached to the nanoparticles during physiochemical synthesis, which in turn limits the biomedical applications of the resulting nanoparticles [18] [18].. The biological synthesis of nanoparticles has several advantages, including rapid and ecofriendly production methodologies and the cost-effective and biocompatible nature of synthesized nanoparticles. Additionally, it does not require further stabilizing agents because plant and microorganism [19].. Moreover, the surfaces of constituents themselves act as capping and stabilizing agents [19] biological nanoparticles progressively and selectively adsorb biomolecules when they contact
complex biological uids, forming a corona that interacts with biological systems. These corona layers provide additional ef cacy over bare biological nanoparticles [72] [72].. Thus, biological nanoparticles are more effective due to the attachment of biologically active components on the surface of synthesized nanoparticles from the biological sources, such as plants and microorganisms. Especially in medicinal plants, there are abundant metabolites with pharmacological activity that are hypothesized to attach to the synthesized nanoparticles, providing additional [19,73,74].. Th The e additional advantage of benet by enhancing the ef cacies of the nanoparticles [19,73,74] the biological synthesis of nanoparticles is that it can reduce the number of required steps, including the attachment of some functional groups to the nanoparticle surface to make them [18].. biologically active, an additional step required in physiochemical synthesis [18]
In addition, the time required for biosynthesizing nanoparticles is shorter than that for physiochemical approaches. Many researchers have developed rapid synthetic methodologies with high yields by utilizing various plant sources. For instance, silver nanoparticles have been synthesized using various plant extracts within 2 min [75] [75],, 5 min [76] [76],, 45 min [44] [44],, 1 h [46] [46],, [45].. Gol old d nanoparticles have also been demonstrated to be synthesized within 3 min and 2 h [45] [44] [44],, 5 min [45] [45],, and 10 min [46] [46],, highlighting the simple and fast synthesis of nanoparticles using plant extracts [75] [75]..
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Biological nanoparticles have been applied in many biomedical contexts, including anticancer and antimicrobial applications because of the higher ef cacy of biological nanoparticles compared with physiochemical nanoparticles for biomedical applications. For instance, Mukherjee et al. showed the better ef cacy of biological silver nanoparticles derived from Olax scandens leaf in terms of anticancer activity, biocompatibility for drug delivery, and imaging facilitator activity
compared with chemically synthesized silver nanoparticles [77] [77].. Furthermore, biological nanoparticles showed high anticancer activity in the cancer cell lines A549 (human lung cancer), B16 [77].. Additionally, biological nanoparticles (mouse melanoma), and MCF7 (human breast cancer) [77] are more biocompatible with the rat cardiomyoblast normal cell line (H9C2), human umbilical vein endothelial cells (HUVEC), and Chinese hamster ovary cells (CHO), than chemically synthesized nanoparticles, which further supports the future applications of biological nanoparticles as drug delivery carriers. Moreover, biological nanoparticles show bright-red uorescence inside cells, which could be utilized to detect the localization of drug molecules inside cancer cells (a diagnostic approach) [77] [77]..
El-Kassas et al. showed the cytotoxic activity of biological gold nanoparticles with an extract of [63].. Nethi et al. the red seaweed Corallina of cinalis c inalis on the MCF7 human breast cancer cell line [63] developed novel proangiogenic biosynthesized gold nanoconjugates to accelerate the growth of new blood vessels through redox signaling [78] [78].. Wang et al. showed the in vivo self-bioimaging of tumors through uorescent gold nanoclusters that were spontaneously biosynthesized by cancerous cells [i.e., HepG2 (a human hepatocarcinoma cell line) and K562 (a leukemia cell line)] [79].. Mukherjee et al. demonstrated a biosynthetic approach for the fabrication of gold nano[79] bioconjugates using Olax scandens leaf extract and applied to lung (A549), breast (MCF-7) and colon (COLO 205) cancer cell lines. These results showed the signicant inhibition of cancer cell proliferation and uorescence imaging in A549 cancer cells [80] [80].. Pa Patr tra a et al. demonstrated the better biocompatibility of biological gold and silver nanoparticles in the HUVEC and ECV-304 cell lines compared with chemically synthesized nanoparticles. Furthermore, biological nanoparticles combined with a drug, doxorubicin, were shown to have a higher anticancer effect in the B16F10 cell line compared with the same drug combined with chemical nanoparticles [81] [81].. Other examples includes gold and silver nanoparticles derived from the leaf extract of the medicinal plant, Butea monosperma monosperma,, which were found to be stable and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2, and A549). In addition, by combining with doxorubicin, the gold and silver nanoparticles showed signicant inhibition of cancer cell proliferation (B16F10, MCF-7) compared
[64].. The possible anticancer with that of chemically synthesized nanoparticles and isolated drug [64] mechanism of nanoparticles is related to their size and shape, which are associated with the generation of reactive oxygen species (ROS), causing damage to cellular components [82] [82].. Additionally, nanoparticles may result in apoptosis via mitochondria-dependent and caspasedependent pathways [76] (Figure S1 in the supplemental information online).
For antimicrobial applications, investigations also showed the higher antimicrobial activity of biologically synthesized nanoparticles compared with physicochemically mediated nanoparticles. Mukherjee et al. demonstrated that biological nanoparticles showed 96.67% antibacterial activity at 30 mM, whereas the chemically synthesized nanoparticles did not show any signicant ef cacy at the same concentration. Sudhasree et al. proposed that the biological nanoparticles from Desmodium gangeticum are more monodispersed and have higher antioxidant, antibacterial, and biocompatible activities in LLC PK1 (epithelial cell lines) compared with chemically [83].. Mohammed et al. also described how biologically synsynthesized nickel nanoparticles [83] thesized zinc nanoparticles have more antimicrobial potential against Salmonella typhimurium ATCC 14028, B. subtilis ATCC 6633, and Micrococcus luteus ATCC 9341 compared with chemically synthesized zinc nanoparticles [84] [84].. The exact antimicrobial mechanism is still under debate, although there are various proposed mechanisms of action for nanoparticles, including
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disturbance of the cell membrane; alteration of cellular DNA and proteins, electron transport, nutrient uptake, protein oxidation, or membrane potential; or the generation of ROS, which lead to cell death (Figure S1 in the supplemental information online).
In addition to their anticancer and antimicrobial activities, biological nanoparticles have also been
proven to be more effective in designing sensors. For example, biogenic silver nanoparticles were successfully used in the fabrication of an optical ber-based sensor for the detection of [85].. H2O2 that is cost effective and portable and can be used in various industrial applications [85] Furthermore, based on the higher ef cacy and biocompatable nature of biological metal nanoparticles, it has been hypothesized that biological nanoparticles may improve the action of a typical anticancer drug by facilitating drug delivery to specic cel cells ls,, which reduces the required drug dosage and avoids the adverse effects of a high amount of drug. Moreover, biological nanoparticles can replace physicochemically synthesized gold and iron nanoparticles in photoimaging and thermal therapies. Furthermore, biological nanoparticles could be used in cosmetic and medical appliances (Figure 1 ).
Concluding Remarks and Prospects
The potential of using metal nanoparticles in various elds increases the need to produce them on an industrial scale and in stable formulations with environmentally friendly processes. Therefore, much effort is being made towards exploiting natural resources and implementing biological synthesis methods with proven advantages, such as being environmentally friendly, easy to scale up, and cost-effective; thus, the green production of nanoparticles using biological resources has great potential. The biological route of synthesizing nanoparticles has many advantages, such as the stable production of nanoparticles with controlled sizes and shapes, the lack of subsequent complex chemical synthesis, the lack of toxic contaminants, and the ability for rapid synthesis using numerous medicinal plants and microorganisms.
to understand how active groups from biological sources attach to the nanoparticle surface, and which active groups are involved, to produce nanoparticles with higher ef cacy. Thus, the plethora of microorganisms and plants that have been successfully used for the biological synthesis of metal nanoparticles prompts the deeper exploration of biological nanofactories to meet the need for nanoproducts in various elds (see Outstanding Questions). However, issues relating to the biomedical applications of biological nanoparticles, including the distribution prole, excretion, and clearance of nanoparticles in in vivo trials, need to be addressed. Additionally, investigations into the biocompatibility and bioavailability of nanoparticles are still at early stages, and considerable research is needed in this direction.
Is the there re anystrat anystrategyby egyby which c h theproblem lem of po poly lydi disp sper erse sed d na nano nopa part rtic icle les s dur during ing bio biolog logica icall syn synthe thesis sis canbe easeasily avoide avoided? d? Why does the ef cacy cacy of bi biol olog ogic ical ally ly act active ive metal metal nan nanopa opartic rticles les depend depend on th the e size size an and d sh shap ape e of na nano nopa parti rticles c les? ? Wh What at is th the e exac exactt mech mechan anis ism m be behi hind nd the biolog biologica icall ef cacy of nanop nanoparticl articles, es, pa part rtic icul ular arly ly th the e hi high gher er ef c a ac c y o f b io logicall nanop logica nanoparticle articles? s?
Ev Even en th thou ough gh bi biolo ologi gica call na nano nopa parti rticles c les are more more biocom biocompat patibl ible e tha than n phy physic sicoochemic cally ally synthesized synthesized nanoparticl nanoparticles, es, wha whatt are the fut future ure app applic licati ations ons of biobiologica logicall nan nanopa opartic rticles les in hum humans ans? ?
Although biological nanoparticles have be been en foun found d to be more more ph phar arma maco colo logi gi-call callyy acti active ve,, wh whic ich h activ active e grou groups ps from from bi biol olog ogic ical al sour source ces s atta attach ch to nano nanopa parrticles and enhance enhance their pharma pharmacolog cologiical act activi ivity? ty?
Ho How w do does es th the e na nano nopa part rtic icle le yiel yield d di diff ffer er with with di diff ffer eren entt bi biol olog ogic ical al sour source ces s an and d the sam same e metal metal salt salt concen concentra tratio tion? n?
The ef cien cientt pr prod oduc ucti tion on of na nano nopa parrticle ticles s usin using g va vario rious us micro microor orga gani nism sms s and plants plants nee needs ds to be optimi optimized zed,, par par-ticu ticula larl rlyy for for in indu dust stri rial al pr prod oduc ucti tion on.. Is th ther ere e an anyy limit limitat atio ion n to usin using g bi biolo ologi gica call sources?
Importantly, the yield of synthesized nanoparticles corresponding to the metal salt concentration and the available biological resources remains to be elucidated, and the parameters that can overcome the problems of polydispersity of biological nanoparticles still require optimization in various biological systems. Furthermore, the lack of knowledge of the chemical components responsible and the underlying mechanisms for the synthesis, action, and stabilization of biological nanoparticles, remain open challenges in taking advantage of plants and microorganisms for nanoparticle synthesis. Especially in terms of biocompatibility, it is important
th thes esis is an and d th thei eirr ef cacy.
Although many reports demonstrate the adv advant antage ages s of produc producing ing nanopa nanoparrticles ticles using using bio biolog logica icall sou source rces, s, severa severall unr unreso esolve lved d issues issues remain remain,, wit with h regard regard to optimiz optimizati ation on yield yield of bio biolog logica icall syn syn--
Outstanding Questions
Whatt det Wha determ ermine ines s the cytoto cytotoxic xicity, ity, biobiodistrib distributi ution, on, and excret excretion ion of nan nanopa oparrticles in vivo? vivo?
Acknowledgments ents Acknowledgm This work was supported by funds from the Ministry of Science and Technology (MOST), The People's Republic of China (2015DFG325 (2015 DFG32560), 60), and BasicScience Resea Research rch Progra Program m throug through h the Natio National nal Research Research Found Foundation(NRF) ation(NRF) from the Ministry Ministry of Educ Education ation (2013R1A1A (2013R1A1A20644 2064430), 30), Repub Republic lic of Korea(Y-J.K.); and KoreaInstitute of Plann Planning ing & Evaluationfor Evaluationfor Techn Technology ology
in Food, Food, Agr Agricu icultur lture, e, and Forest Forestry ry & Fisher Fisheries ies (KI (KIPET PET NO: 313038 313038-03 -03-2-2-SB0 SB020) 20) (D-C (D-C.Y. .Y.). ).
Supplementary Information
Sup Supple plemen mentar taryy inform informati ation on associ associate ated d wit with h this this articl article e can be fou found nd online online at http://dx.doi.org/10.1016/j.tibtech.2016.02. 006.. 006
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