Biomedical Applications Of Gold Nanoparticles

Murali et al. (2018)E-mail: Central Bringing Excellence in Open Accessbiosensing and labelling. The various types of sensors exploitthe optical properties (light absorption, scattering, fluorescence,reflectance, Raman scattering, and refractive index) of eitherbulk gold or individual nanoparticles [31]. Gold nanoparticleshave been used as contrast agents in cellular or molecularimaging for a long time. The most common imaging techniques tovisualize the intracellular organelles are an electron and confocalmicroscopy [32]. Owing to their high-electron density AuNP isan established candidate in electron microscopy for a long time.With advancement in technologies, many other methodologieslike TPL imaging, came to deal with AuNPs to locate a target cellor molecule [32]. A novel sensor for the colourimetric detectionof Salmonella typhimurium based colour change effect of goldnanoparticles was developed by Ma et al. [33]. Gold nanoparticleswere functionalized with aptamers capable recognize S.typhimurium which acted as stabilizers for the AuNPs even at highconcentrations of NaCl. In the presence of the S. Typhimuriumbacteria the aptamers present on the nanoparticle surface bind tothe bacteria which results in the aggregation of the AuNPs, thus avisible colour change [33].Gold nanoparticles are extensively used in biosensingapplications these days [21,22]. Determination of blood glucoselevel [34], detection of bacteria [35], viruses etc, detection ofpollutants [36] and monitoring pathogens [37] can be effectivelycarried out by biosensing. A biosensor provides selectivequantitative or semi-quantitative analytical information usinga biological recognition element. Biological molecules suchas antibodies, carbohydrates, nucleic acids, enzymes, etc., areemployed as biological recognition elements. The generalprinciple of a biosensor is associated with the transformationof changes associated with the binding of the analyte to thebioreceptors into optical, electrical or qualitative output signalswith different signal transducers [38]. AuNPs can be effectivelyused in various biosensors as transducer due to its nobleoptoelectronic properties. The various roles that AuNPs play indifferent biosensors are listed in Table 1 [38].A peculiarity of current use of the electron microscopictechnique is the application of high-resolution transmissionelectron microscopes and systems for the digital recording andprocessing of images. The major application of immunoelectronmicroscopy in present-day medical and biological research is theidentification of infectious agents and their surface antigens [21].The techniques often employed for the same purposes includescanning atomic-force, scanning electron, and fluorescencemicroscopes [21].For optical biosensing utilizing AuNPs, the optical propertiesprovide a wide range of opportunities, all of which ultimatelyarise from the collective oscillations of conduction bandelectrons (‘‘plasmons’’) in response to external electromagneticradiation. The most common optical sensing modalities forAuNP is the surface plasmon resonance (SPR) which in simplewords is optical phenomenon arising from the interactionbetween an electromagnetic wave and the conduction electronsin themetal. Apart from SPR-based biosensors, AuNPs are alsoincorporated into other optical structures, like, interferometerbased biosensors [21]. Rosana AS and coworkers developed ananostructured piezoelectric immunosensor for detection ofJSM Nanotechnol Nanomed 6(1): 1064 (2018)human cardiac Troponin T. Anti-human troponin T (anti-TnT)antibodies were covalently immobilized on the nanostructuredelectrode surface by thiol-aldehyde linkages [39]. In a solution,anti-TnT fixed in the QCM electrode capture TnT [39]. There is alsogold nanoparticle related electrochemical biosensors made bycoupling biological recognition elements with gold nanoparticlemodified electrochemical transducers. Gold nanoparticles canbe deposited onto the transducer surface using electrochemicalmethods or by physical attachment procedures.PHOTOTHERMAL THERAPYPhotothermal therapy is an effective therapeutic technique totreat diseases like cancer. Here nanoparticles incorporated intotumour cells generate heat in response to light which is suppliedexternally. AuNP is widely employed for PTT because of avariety of reasons. These reasons are mentioned in the followingsentences. AuNPs offer a variety of advantages including:(1) Biocompatible nature with less cytotoxicity.(2) Tiny dimensions that allowtumour penetration uponsystemic delivery,(3) Simple chemistry for the attachment of biomolecules,(4) Light-to-heat conversion, and(5) Tunability to absorb NIR light, that enters cells moreefficiently.One of the greatest benefits of PTT in cancer therapy, whencompared with other conventional therapies, is the specificityof the treatment. Other techniques are unspecific in nature thatultimately leads to the destruction of the healthy cells along withthe cancerous cells. In order to use for photothermal therapy,AuNPs must fulfil certain criteria, and properties like AuNPsused in photothermal applications must meet several propertiessuch as having plasmon resonance tunability, high photothermalconversion efficiency, and simple surface functionalizationor encapsulation chemistry. Based on these design criteria,nanoshells (NSs), nanorods (NRs), nanocages (NCs), andnanostars have emerged as the most common photothermaltransducers. Huan li et al. [40], have an interesting work reporton “mixed-charge self-assembled monolayers” as a facile methodto design pH-induced aggregation of large gold nanoparticles fornear-infrared photothermal cancer therapy. They introduced afacile way to endow gold nanoparticles (AuNPs) especially thoselarge ones with tunable pH-aggregation behaviours by modifyingthe nanoparticle surface with mixed-charge self-assemblymonolayers (SAMs) compromising positively and negativelycharged thiol ligands [40]. Figure 4 represents the schematicillustration of MC-AuNPs aggregation in a tumour acidic pHinduced manner for photothermal cancer therapy.PHOTODYNAMIC THERAPYPhotodynamic therapy (PDT), has been utilized forthe treatment for a spread of oncological, cardiovascular,dermatologic and ophthalmic diseases. It includes a mix of 2basic therapeutic elements: a photosensitizer (PS) drug anda nonthermallight. Light irradiation elevates ps to an excitedstate where this energy is later transferred to molecular oxygento form reactive oxygen species (ROS), primarily composed3/6

Murali et al. (2018)E-mail: Central Bringing Excellence in Open AccessFigure 3 (a) TEM image of a Listeria monocytogenes cell labeled with an antibody-colloidal gold conjugate(b) A scanning atomic-force microscopy image of tobacco mosaic virus labeled with an antibody- colloidal gold conjugate [21].Figure 4 Schematic illustration of MC-AuNPs aggregation in a tumor acidic pH-induced manner for photothermal cancer therapy [40].Table 1: Different functions of AuNPs in Biosensor systems [38].Principle ofTypes of biosensorsFunctions of GNPsdetectionOptical ensorChanges in opticalpropertiesEnhancement ofrefractive indexchangesEnhancement ofelectron transferChanges atalysis of reactionsChanges in massBiomoleculeImmobilization,amplification of masschangeJSM Nanotechnol Nanomed 6(1): 1064 (2018)Properties usedSensoradvantageslarge dielectricconstant, high density,high molecular weightConductivity, vityBiocompatibility, largesurface areaHigh surface ty, highdensity, Large surfaceto-volume ratioImprovedsensitivity andstabilityImprovedsensitivity andselectivityImprovedsensitivityTypical examplesDNA sensor with GNPs responses1000 times more sensitive thanwithoutElectron transfer rate of 5000 persecond with GNPs, while 700 persecond without GNPsGlucose biosensor with GNPsachieves detection limit of 0.18 µMNADH sensor based on GNPs shows780 mV over potential decreasewithout any electron transfermediatorsDNA sensor using GNPs asamplification tags with detectionlimit of 10-16 mol/L4/6

Murali et al. (2018)E-mail: Central Bringing Excellence in Open Accessof singlet oxygen, then induces each apoptosis and necrosisthat ultimately leads to the destruction of affected cells. Lackof suitable PS is limiting the use of PDT to emerge into themainstream for cancer treatment, blessed with its superioroptoelectronic properties, biocompatible nature, and high scopeof surface functionalization, AuNPs can be an effective candidateas a ps. Yaminyang and coworkers [41] found out that AuNPs canenhance 5-aminolevulinic acid (5-ALA)-induced ROS formationand the enhancement is size-dependent and can be furtherimproved by the intracellular formation of gold nano-aggregates,which suggest that plasmonic AuNPs may amplify photonicenergy absorbed and then transfer the energy to neighboringPSfor enhancing ROS formation [41].Maldonado-Alvarado Elizabeth et al. [42], determined theefficiency of PDT using AuNPs and protoporphyrin IX (PpIX)induced and not induced by the aminolevulinic acid (ALA). It wasfound the conditions of synthesis of hydrosoluble AuNP and werecharacterized by transmission electronic microscopy (TEM)and UV-VIS spectroscopy. It was realized a kinetic by TEM todetermine the cellular incorporation time of AuNP, the maximumincorporation of np-Au was 16 h. PDT was applied using differentdoses of np-Au and photosensitizers. It was observed that the useof PDT simultaneously with AuNP did not increase the mortalityof HeLa cells [42]. The adoption of functionalized Au NPs incurrent cancer PDT represents a promising strategy to enhancetherapeutic effectiveness and improve treatment selectivity.Targeted delivery of Au NPs into mitochondria provides vitalsteerage and critical proof on the effectiveness of intracellulartargeting for any optimisation of drug delivery and improvementof therapeutic efficaciousness. Additionally, the surface plasmonicresonance of AuNPs will be extended to the near-infrared rangeby calibrating their structures, probably enabling PDT with deeplight penetration [42].CONCLUSIONOwing to the success of the fast development of technologiesfor the chemical synthesis of AuNPs throughout the past decade,investigators presently have at their disposal a colossal diversityof accessible particles with needed parameters in respect ofsize, shape, structure, and optical properties. Moreover, thequestion that currently on the agenda is that the primarymodeling of a nanoparticle with desired properties and alsothe subsequent development of a procedure for the synthesisof a theoretically foreseen nanostructure. Gold nanoparticles(AuNPs) are comparatively inert in the biologicalatmosphereand have a number of physical properties that are appropriatefor many biomedical applications. The current uses of AuNPs inthe biomedical field include photothermal therapy, drug delivery,photodynamic therapy, gene therapy, biolabelling, photodynamictherapy, biosensing, etc. It is ought to be stressed that AuNPsare biodegradable. Therefore, the biodistribution and excretiondynamics have to be compelled to be studied comprehensivelyfor various animal models. Because the excretion of accumulatedparticles from the liver and spleen will take up to 3-4 months, thequestion on the injected doses and doable inflammation processescontinues to be of vital importance. Bioaccumulated AuNPs willinterfere with completely different diagnostic techniques, oraccumulated AuNPs will exhibit catalytic properties. All theseJSM Nanotechnol Nanomed 6(1): 1064 (2018)concerns, in conjunction with potential toxicity, are massivelimitations of AuNPs on a successful clinical translation.In summary, there should be more effort for an effectiveresearch a to establish correlations between the particleparameters (size, shape, and functionalization with variousmolecular probes), the experimental parameters (model; doses;method and time schedule of administration; observation time;organs, cells and sub

AuNP is the surface plasmon resonance (SPR) which in simple words is optical phenomenon arising from the interaction between an electromagnetic wave and the conduction electrons in themetal. Apart from SPR-based biosensors, AuNPs are also incorporated into other optical structures, like, interferometer-based biosensors [21].