A vaccine in action: the introduction of an antigen of a pathogen in blood stream left stimulates the production of antibodies against the pathogen middle ; so that in case of infection by the actual pathogen right ; the immune system is ready to fight the disease adapted and redrawn from Mayo Clinic Foundation for Medical Education and Research.
Cellular specific immunity is also elicited by gold nanoparticles vaccines, such as those protecting against listeriosis see Section 6. Usually nanoparticles are synthesized in colloidal solution by reduction of chloroauric acid HAuCl 4 by variations of the so-called Turkevich method [ 46 ]. Their characterization is carried out by ultraviolet-visible spectroscopy, their diameters determined by transmission electron microscopy.
Then, they can be further functionalized with the desired molecules, according to their specific needs. One example is given in Scheme 1 , showing a procedure carried out by Saha et al. Gold nanoparticles were synthesized in aqueous medium by an ultra-sound assisted green method using black pepper extract and chitosan as reducing agent and a stabilizing agent, respectively.
The biopolymer-inspired biogenic method Scheme 1 was found to be stable and with enhanced bioactivity. The developed nanomaterial boosts the production of reactive oxygen species and misbalances the antioxidant parameters of detoxification enzymes of filarial parasites, such as GST, which besides its immune prophylactic potency, is also a promising candidate vaccine as shown in S. Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [ 8 , 9 , 10 , 11 , 12 , 15 , 20 , 21 , 26 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ].
Their shape and size can affect immunological responses in vivo and in vitro [ 51 , 62 , 63 , 64 , 65 ]. Moreover, they are able to penetrate blood vessels and tissue barriers and to be targeted to a specific cell by means of specifically functionalized molecules [ 59 ]. Moreover, gold nanoparticles can be packaged inside virus-like particles generated by heterologous expression of viral structural genes that are powerful tools in vaccine development [ 66 ].
A positively charged antigen and a negatively charged immuno-adjuvant on gold nanoparticles resulted in a new vaccine platform. Ultrasmall graphene oxide-supported gold nanoparticles usGO-Au were obtained from reduction of chloroauric acid using usGO and then decorated with ovalbumin antigen OVA through physical adsorption to obtain usGO-Au OVA and used immune adjuvants [ 70 ].
Fluorescent Au nanoclusters were synthesized using ovalbumin-CpG oligodeoxynucleotides ODNs conjugates as templates [ 71 ]. The nanoclusters can act as self-vaccines to assist in generation of high immunostimulatory activity.
Gold-based nanovaccines were synthesized using a self-assembling conjugation method [ 53 ]. Dendritic cells uptake gold nanovaccines with minimal toxicity and are able to process the vaccine peptides on the particles to stimulate cytotoxic T lymphocytes CTLs.
These high-peptide density Au nanovaccines can stimulate CTLs better than free peptides and have great potential as carriers for various vaccine types [ 53 ]. Hydrophilic gold nanodots were used to control lipopolysaccharide assembly to ease the formation of stable endotoxin nanovesicles, which are stable precursors of cubosomes and hexosomes with specific immunological effects that might be useful in vaccine development [ 72 ].
Needle-free vaccine delivery systems efficiently transport powdered or particulate DNA and protein vaccines into the epidermal tissue [ 73 , 74 , 75 , 76 ]. A solid-in-oil dispersion of gold nanorods can also enhance transdermal protein delivery and skin vaccination [ 77 ]. Plasmid DNA pDNA -coated gold nanoparticles were successfully delivered into ex vivo murine and porcine skin at low inlet pressures using parallel arrays of microchannels [ 78 ].
It was shown that full-length pDNA was preserved after each particle preparation and jetting procedures. Below, several examples are given on the role of gold nanoparticles in the attempts of producing vaccines for several diseases. Cancer is one of the main causes of death worldwide, that can affect people at all ages, even small children and foetuses, the risk usually increasing with age [ 32 , 79 ].
The present treatments consist of surgery, chemotherapy, or radiotherapy, which can have adverse side effects, due to a lack of specificity for tumors [ 80 ]. An ideal treatment should aim only at the target tumor cells and have limited detrimental effects on normal cells [ 32 , 79 ]. It was first postulated by Coley in that the immune system was able to recognize and set a response against tumors [ 81 ].
Later, it was shown that immunization of mice with mutated tumor cells could induce a protective anti-tumor immune response against non-immunogenic tumor [ 32 ]. This led to cancer immunotherapy research and to the development of cancer vaccines capable of generating an active tumor-specific immune response.
Cancer vaccines have high specificity for tumor cells and long-lasting immunological memory that may safeguard against recurrences, and can be used to either prevent prophylactic or treat established cancer therapeutic [ 32 , 79 ].
Therapeutic cancer vaccines also called active immunotherapy work to enable the immune system of a patient to eradicate cancer cells [ 82 ]. Identification of tumor-associated antigens TAAs and tumor-specific antigens TSAs has led to increased efforts to develop vaccination strategies. Vaccines may be composed of whole cells or cell extracts, genetically modified tumor cells, dendritic cells DCs loaded with TAAs, immunization with soluble proteins or synthetic peptides, recombinant viruses or bacteria encoding tumor-associated antigens, and plasmid DNA-encoding TSAs or TAAs in conjunction with appropriate immunomodulators [ 32 , 79 ].
All of these vaccination approaches aim to induce specific immunological responses and are localized into TAAs, destroying only the tumor cells and leaving the majority of other cells of the body undamaged. An efficient delivery to cells is needed and gold nanoparticles have proved to be excellent carriers [ 83 , 84 , 85 , 86 , 87 , 88 , 89 ].
Gold nanoparticles enabled efficient antigen delivery to dendritic cells and then activated the cells to facilitate cross-presentation, inducing antigen-specific cytotoxic T-lymphocyte responses for effective cancer therapy [ 88 ]. Moreover, they show several advantages over other nanoparticulate-based carriers, such as the ease with which they control their size for different applications, the variety of antigens and adjuvants that can be easily linked to and displayed on their surface, the fact that they can be detected using non-invasive imaging techniques, providing clinicians with information on where or whether the vaccines have been delivered, which helps to predict or evaluate therapeutic efficacy, and the biocompatibility and non-toxicity of gold [ 86 , 87 , 90 ].
Au nanoparticle immunotherapies are well suited for synergistic combination therapy with existing cancer therapies such as photothermal ablation [ 59 , 87 ]. The several functionalities of gold nanoparticles make them promising vehicles for immune therapies, especially for combinatorial treatment approaches that target multiple immune pathways Figure 3.
Applications of gold nanoparticles in cancer immunotherapy adapted and redrawn from [ 87 ]. A polymerizable version of the Tn-antigen glycan was synthesized and the polymers were conjugated to gold nanoparticles, producing nanoscale glycoconjugates [ 91 ]. These nanomaterials generated a strong and long-lasting production of antibodies, selective to the Tn-antigen glycan and cross-reactive toward mucin proteins displaying Tn, and thus represent a simple approach to the synthesis of anticancer vaccines.
MUC-1 is involved in fundamental biological processes that can be found over-expressed and with a clearly changed glycan pattern on epithelial tumor cells, and thus is a promising target structure in the search for effective carbohydrate-based cancer vaccines and immunotherapeutics [ 58 ].
Other authors also reported on the synthesis of MUC1-glycopeptide antigens and their coupling to gold nanoparticles of different sizes and developed a new dot-blot immunoassay to test the potential antigen-antibody binding [ 58 ].
A glycopeptide sequence derived from MUC-1 glycoprotein and the T-cell epitope P30 sequence were immobilized gold nanoparticles attached to polyethylene glycol chains [ 92 ]. After immunization, mice showed significant MHC-II mediated immune responses, and their antisera were able to recognize human MCF-7 breast cancer cells. Gold nanoparticles designed this way have the potential to be used in the development of anticancer vaccines.
Gold nanoparticles proved to be efficient in facilitating the delivery of the ovalbumin OVA peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a BOVA tumor model. Gold nanoparticle-mediated OVA peptide delivery can have important therapeutic benefits without the need of an adjuvant, showing that gold nanoparticles are effective peptide vaccine carriers, having the potential to allow the use of lower and safer adjuvant doses during vaccination [ 93 ].
The use of gold nanoparticles in HIV vaccine development has been recently reviewed by several authors [ 94 ]. After more than 30 years since the discovery of HIV in , no effective vaccine is yet available [ 24 , 95 , 96 , 97 ]. Some histocompatibility complex molecules expressed on the surface of HIV are potential targets for neutralizing antibodies [ 98 ], as shown in Figure 4. Among the few broadly neutralizing HIV monoclonal antibodies, 2G12 is the only carbohydrate-directed that is able to recognize a cluster of high-mannose glycans on the viral envelope glycoprotein gp [ 95 ].
This type of glycan is thus envisaged as a target to develop an HIV vaccine capable of eliciting 2Glike antibodies. Thiol-terminated oligosaccharides have been attached on gold nanoparticles and have been used in attempts to develop an HIV vaccine [ 99 ]. Two nanometer gold glyconanoparticles were coated with synthetic partial structures of several mannosides [ ]. The assembly of the antennas of the gp high-mannose type glycan on gold glyconanoparticles provided superior binding to the anti-HIV antibody 2G12, which could help in the design of a carbohydrate-based vaccine against HIV.
It was shown that conjugation to negatively charged gold glyconanoparticles could stabilize either the alpha-helix or beta-strand conformation of the third variable region V3 peptide of the HIV-1 gp [ ]. The peptide on the nanoparticles shows more stability toward peptidase degradation compared to the free peptide.
V3 beta-glyconanoparticles produce antibodies in rabbits that recognize a recombinant gp, and the serum showed consistent neutralizing activity.
These results potentially allow for the design of new fully synthetic HIV vaccine candidates [ ]. Gold nanorods modified with poly diallydimethylammonium chloride or polyethyleneimine can significantly promote cellular and humoral immunity, as well as T-cells proliferation, through activating antigen-presenting cells, when compared to naked HIV envelope plasmid DNA treatment in vivo [ ].
The use of gold nanoparticles in designing vaccines against tick-borne encephalitis TBE was proposed for the first time by Demenev et al. The vaccine was prepared by conjugating colloid gold with a soluble TBE antigen.
In animals immunized with the experimental vaccine, the protection coefficient and mean survival time were, respectively, 1. Moreover, the mean survival time was 1. In a more recent study, colloidal gold particles were used as carriers of protein antigen of the capsid of the TBE virus in the antiviral vaccine [ ]. Japanese B encephalitis vaccine is an important vaccine to prevent this serious mosquito-borne disease caused by the virus [ , ].
There are some semiquantitative methods to determine this vaccine, such as plaque forming unit and the animal testing, but they have low sensitivity, are time-consuming, and have a high cost.
A label-free amperometric immunosensor for fast and sensitive assay of Japanese B encephalitis vaccine was reported with a specific response in the range 1. It exhibited fast potentiometric high sensitivity and long-term stability.
These works are promising test methods for biological products. Hepatitis is inflammation of the liver that may originate a yellow color in the skin and eyes and abdominal pain, among other symptoms that can be caused by viruses or from the abuse of alcohol and certain medications.
Hepatitis A and E are often spread by contaminated food and water, while hepatitis B is mainly sexually transmitted but may pass from mother to child during pregnancy. Types B and C are usually spread through infected blood. Hepatitis D can only infect people already infected with hepatitis B.
Figure 5 shows a comparison between the viruses. Concerning hepatitis B vaccine research, HBsAg-DNA can be introduced into the host by intramuscular or intradermal route using a needle with syringe.
Micron-size gold particles were used as particulate adjuvants and coinjected intradermally with plasmid DNA encoding the HBsAg into mice [ , ]. The presence of gold particles accelerated the antibody response significantly, increased the percentage of responding animals, and shortened the time taken to reach maximal antibody titers by two weeks. These immunizations were effective in protecting mice against tumor challenge with cancer cells, expressing HBsAg as a surrogate cancer antigen.
Good results were also obtained with minipigs [ ]. Electrically activated plasmonic Au nanoparticles can drive vibrational and dipole-like oscillations that are able to disrupt nearby cell membranes, allowing enhanced cell poration and facilitating the uptake of a model hepatitis C virus DNA vaccine was recently reported [ ].
Immunized mice showed up to fold higher gene expression compared to control treatments without nanoparticles and exhibited significantly increased levels of both antibody and cellular immune responses.
A new method of preparation of a vaccine for hepatitis E HEVA using in situ easy growth of gold clusters in the vaccine was recently reported [ ]. The fluorescence of gold clusters enables the HEVA to be traceable, which may open a way to track the dynamic behavior of vaccines and further help to optimize an individual therapeutic regimen for immunotherapy [ ]. Gold has been used in several other vaccines. Some examples are reported below.
Gold nanoparticles were conjugated to a synthetic peptide of the VP1 capsid protein of the foot-and-mouth disease virus, which causes an acute, highly contagious infection of domestic and wild animals, transmittable to humans, for which the existing vaccines are not much effective [ ]. Gold nanoparticles were evaluated as vaccine carriers for enhancing the antibody response against a resembling foot-and-mouth disease virus peptide [ 62 ]. Particles with 8—17 nm in diameter stimulated the highest antibody levels and accumulated at the highest numbers in the spleen of mice.
Recently, the potential of chitosan functionalized gold nanoparticles CsAuNPs for the transmucosal delivery of tetanus toxoid vaccine was shown [ 63 , , ]. Excellent stability was found for the formulation at recommended storage conditions. The synthesized CsAuNPs were spherical, around 40 nm in size and conferred protection to TT against gastric hydrolysis. Gold glyconanoparticles proved to be good carriers for a synthetic Streptococcus pneumoniae type 14 conjugate vaccine [ 50 ].
A gold nanorod construct that displayed the major protective antigen of the respiratory syncytial virus which causes pneumonia and wheezing in children and the elderly , the fusion protein F was reported, which can be a candidate vaccine preparation by the covalent attachment of viral protein using a layer-by-layer approach [ ].
Gold nanoparticles of 12 nm were conjugated to the matrix 2 protein M2e of influenza A virus M2e through thiol—gold interactions [ ]. This virus Figure 6 is often responsible for seasonal epidemics and is also a high risk for pandemics [ ]. Vaccination of mice with M2e-Au conjugates induced M2e-specific IgG serum antibodies, which significantly improved by addition of CpG as adjuvant, as mice immunized that way were fully protected against lethal PR8 [ ]. The same authors also showed that the inclusion of excess soluble M2e antigen along with M2e immobilized on Au nanoparticles is vital for inducing high levels of antibody response, and in providing complete protection [ ].
A recent study showed that animals immunized with a transmissible gastroenteritis virus, conjugated with colloidal gold nanoparticles, produced antibodies with a higher titer than those produced in response to the native virus [ ]. A gold nanoparticle antigen delivery approach was used together with a novel polysaccharide nanoparticulate adjuvant, and an effective T-cell vaccine was developed providing protection in animal models of listeriosis a fatal infection for fetuses and newborns that causes meningitis and cutaneous lesions [ ].
This antigen delivery approach against listeriosis, using gold nanoparticles and bacterial peptides, elicits protective cellular immunity, independent of the adjuvant used, either as a carbohydrate such as Advax [ ] or a TLR-4 agonist such as DIO-1 [ ]. Gold glyconanoparticles loaded with listeriolysin peptide LLO or glyceraldehydephosphate dehydrogenase peptide GAPDH were successfully administrated to pregnant female mice as a vaccination for this disease [ ].
Neonates from vaccinated mothers were free of bacteria and healthy, while non-vaccinated mice showed clear brain affections and cutaneous diminishment of melanocytes.
Amphiphilic surface ligand-coated Au nanoparticles able to target myeloid dendritic cells in lymph nodes were used as a peptide antigen carrier, increasing the efficacy of a model vaccine in BOVA melanoma mouse models [ ]. The sera raised against F1-antigen coupled to Au nanoparticles were able to competitively bind to recombinant F1-antigen, displacing protective macaque sera.
The codon-harmonized recombinant Pfs25 in Escherichia coil CHrPfs25 is able to produce malaria transmission-blocking antibodies in mice. CHrPfs25 was also investigated, with gold nanoparticles of different shapes, size and physicochemical properties as adjuvants for induction of transmission blocking immunity, causing transmission blocking antibodies [ ].
These results show that gold nanoparticle-based formulations can be developed as nanovaccines to enhance the immunogenicity of vaccine antigens. Gold nanoparticles were conjugated to N-terminal domains of Pseudomonas aeruginosa flagellin recombinant protein through direct interaction of thiol molecules of the cysteines with gold and formation of Au—S bond [ ]. Synthetic virus-like particles sVLPs were prepared by incubating nm gold nanoparticles in a solution containing an avian coronavirus spike protein [ ].
After removing the free proteins, antigen-laden particles were recovered and showed morphological semblance to natural viral particles. Vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms, and provided superior antiviral protection when compared to a commercial whole inactivated virus vaccine [ ]. Burkholderia mallei are bacteria responsible for the glanders disease, which is recently classified as a Tier 1 agent, since they can be weaponized for aerosol release, cause high mortality rates, and show multi-drug resistance, and for which there is so far no vaccine available [ ].
Gold nanoparticles were covalently coupled with one of three different protein carriers TetHc, Hcp1, and FliC followed by conjugation to lipopolysaccharide LPS generated significantly higher antibody titers compared with LPS alone.
In another study, a gold nanoparticle glycoconjugate composed of Burkholderia thailandensis LPS conjugated to FliC was evaluated for the first time as a candidate vaccine for glanders on rhesus macaques Macaca mulatta [ 57 ].
It has recently been shown that the Pichia pastoris yeast expression system was adequate for the production of recombinant-truncated proteins, and their apparent bioactivity suggests that tORF25, tORF25C, and tORF25D are potential candidate vaccines against Cyprinid herpes virus 2 infection. Found in farmed gibel carp Carassius gibelio , it is an infectious disease that recently emerged in China that has been troubling the aquaculture industry [ ].
Colloidal gold-labelled immunoglobulin was used to confirm Rvc protein localization on Mycobacterium tuberculosis [ ]. These results, along with those obtained for other proteins, might lead to the discovery of select peptides that could have the potential to be included in a subunit-based vaccine for tuberculosis, an infectious disease that remains lethal around the world.
Biocompatible gold nanoparticles were complexed with anti-dengue virus small interfering RNAs siRNA , and were able to enhance the siRNA delivery and stability, becoming a novel strategy against a virus that causes flu-like symptoms, haemorrhagic fever, and death [ ].
Escherichia coli as a model pathogen for the design of an antibacterial vaccine [ ]. The bacterial outer membrane vesicles were collected and successfully coated onto gold nanoparticles with a 30 nm diameter. The resulting bacterial membrane-coated gold nanoparticles, when injected subcutaneously, induced rapid activation and maturation of dendritic cells in the lymph nodes of the vaccinated mice, generated durable antibody responses, and induced a high production of interferon gamma and interleukin, but not interleukin-4, indicating its capability of generating strong Th1- and Thbiased cell responses against the used bacteria.
A monoclonal antibody raised against human cytomegalovirus CMV, a herpes virus surface glycoprotein gB was chemically conjugated with gold nanoparticles [ ]. The gB-gold nanoparticles blocked viral replication, virus-induced cytopathogenic effects, and virus spread in cell culture without inducing cytotoxicity, and cells treated with them gained resistance to CMV infection. As discussed above, research on gold has indicated its potential for several applications in nanomedicine and its bio medical applications, including vaccines, and, as shown in this review, has been increasing.
The overall conclusion is that the potential of gold for stimulating research in vaccines is considerable. The results will certainly lead to more practical and commercial applications, the full extent of which has yet to be envisaged. Certainly, the use of gold carries added costs. As newer and more expensive vaccines are introduced and attempted to reach people of different ages and in new settings, the logistics systems must be strengthened and optimized, as recently highlighted and reviewed by Zaffran et al.
Synthesis of biopolymer-inspired gold nanoparticles reported by Saha et al. The author declares no conflict of interest. The founding sponsors had no role in the design of the review; in the collection, analyses, or interpretation of literature; in the writing of the manuscript; or in the decision to publish the paper. National Center for Biotechnology Information , U. Journal List Molecules v. Published online May Margaret A. Author information Article notes Copyright and License information Disclaimer.
Andreea Catalina Gluhoi, a female gold researcher, who passed away too soon. Received Apr 24; Accepted May This article has been cited by other articles in PMC. Abstract Nowadays, gold is used in nano- medicine, usually in the form of nanoparticles, due to the solid proofs given of its therapeutic effects on several diseases.
Introduction It is well known that gold is inert in the bulk stable and is only active as a catalyst in the form of nanoparticles [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Open in a separate window.
Figure 1. Figure 2. Cancer Vaccines Cancer is one of the main causes of death worldwide, that can affect people at all ages, even small children and foetuses, the risk usually increasing with age [ 32 , 79 ].
Figure 3. Figure 4. Encephalitis Vaccines The use of gold nanoparticles in designing vaccines against tick-borne encephalitis TBE was proposed for the first time by Demenev et al.
Hepatitis Vaccines Hepatitis is inflammation of the liver that may originate a yellow color in the skin and eyes and abdominal pain, among other symptoms that can be caused by viruses or from the abuse of alcohol and certain medications. Figure 5. Other Vaccines Gold has been used in several other vaccines. Figure 6. Future Prospects As discussed above, research on gold has indicated its potential for several applications in nanomedicine and its bio medical applications, including vaccines, and, as shown in this review, has been increasing.
Scheme 1. Conflicts of Interest The author declares no conflict of interest. References 1. Grisel R. Catalysis by gold nanoparticles. Gold Bull. Haruta A. When gold is not noble: Catalysis by nanoparticles. Hashmi A. Gold catalysis. Bond G. Catalysis by Gold.
Carabineiro S. Catalytic Applications for Gold Nanotechnology. In: Heiz E. Gold Catalysis. In: Corti C. Gold: Science and Applications. Priecel P. Anisotropic gold nanoparticles: Preparation and applications in catalysis. Dykman L. Acta Nat. Gold nanoparticles in biomedical applications: Recent advances and perspectives.
Shah M. Biological Applications of Gold Nanoparticles. Maughan C. Particulate inorganic adjuvants: Recent developments and future outlook. Versiani A. Gold nanoparticles and their applications in biomedicine. Future Virol. Robles-Garcia M. Applications of Nanotechnology in the Agriculture, Food, and Pharmaceuticals.
Klinman D. Use of nanoparticles to deliver immunomodulatory oligonucleotides. Wiley Interdiscip. Fujita Y. Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles. Gregory A. Vaccine delivery using nanoparticles. Zhu M. Applications of nanomaterials as vaccine adjuvants. Vaccines Immunother. Marasini N. Oral delivery of nanoparticle-based vaccines. Expert Rev.
Irvine D. Synthetic Nanoparticles for Vaccines and Immunotherapy. Alberto J. Gold nanoparticles and vaccine development. The cleavage of the substrate provides an enzyme-amplified fluorescent readout of the binding event, allowing the identification of proteins even in desalted human urine.
The transport of therapeutic agents to the cells by AuNPs is a critical process in biomedical treatment. Several research groups have used functionalized AuNPs to investigate the interactions with cell membrane to improve delivery efficiency. AuNP therapeutics can be delivered into cells through either passive or active targeting mechanisms. Passive targeting is based on the enhanced permeability and retention EPR effect where the AuNPs will accumulate within the tumor via its irregular vasculature, allowing larger particles to pass through the endothelim.
In one arena, AuNPs have been exploited as attractive scaffolds for the creation of transfection agents in gene therapy to cure cancer and genetic disorders. Mirkin et al. Rotello et al. Lysine-based motif coating AuNPs provided effective non-toxic transfection vectors for DNA delivery that were up to 28 times more effective than polylysine.
B Knockdown of luciferase expression over 4 days. Loading of drugs onto AuNP can be performed through either non-covalent interactions or covalent conjugation. Drug encapsulation with AuNPs has been demonstrated through the use of hydrophobic 65 or hydrophilic 66 pockets generated by the monolayer. In a recent example, Burda et al. C In vivo fluorescence imaging of AuNP-Pc 4 conjugates injected mouse at various time points within 24 hr.
Arrows indicate the tumor location. The cationic surface of the nanoparticles facilitated their penetration through cell membranes and the payload release was triggered by intracellular GSH. Alternatively, Rotello et al. Using AuNPs as therapeutic moieties in their own right is another potential approach for medical treatment. For instance, Feldheim et al.
Recently, Rotello et al. When treated with 1-adamantylamine ADA , the CB[7] is displaced from the nanoparticle surface, releasing the toxic particle from the endosome and killing the cancer cell Scheme 5.
AuNP and surface functionalization, and the use of intracellular host-guest complexation to trigger nanoparticle cytotoxicity. The versatile optical and electronic properties of AuNPs have been employed for cell imaging using various techniques, including computed tomography CT , 78 dark-field light scattering, 79 optical coherence tomography OCT , 80 photothermal heterodyne imaging technique 81 and Raman spectroscopy.
Hainfeld et al. A Schematic of the method for preparing doxorubicin-loaded aptamer-conjugated AuNPs. Evaluation of 10 different multiplexed SERS nanoparticles in vivo. Raman map of 10 different SERS particles injected in a nude mouse. AuNPs have multiple attributes that make them potent tools for the use in bionanotechnology. The wide range of surface functionality and bioconjugates coupled with the outstanding physical properties of AuNPs make these systems valuable for imaging applications.
Moreover, the creation of highly sensitive and selective diagnostic system for target analytes can be achieved by engineering their surface monolayer. AuNP-based delivery vectors have also shown promise in therapeutics with their high surface loading of drug and gene as well as the controllable release of the payloads. Taken together, AuNPs are incredibly versatile materials for next-generation biomedical applications. B Limitation of detection of E.
At the top, microplate wells show the color change upon variation of the bacteria concentration. Kinetic absorbance responses upon addition of different bacteria concentrations are shown. National Center for Biotechnology Information , U. Author manuscript; available in PMC Jul Author information Copyright and License information Disclaimer.
Copyright notice. The publisher's final edited version of this article is available at Nanoscale. See other articles in PMC that cite the published article. Abstract Gold nanoparticles AuNPs are important components for biomedical applications. Introduction Gold nanoparticles AuNPs have been widely employed in bionanotechnology based on their unique properties and multiple surface functionalities.
Open in a separate window. Scheme 1. Synthesis of gold nanoparticles A wide array of solution based approaches has been developed in the past few decades to control as the size, 8 shape, 9 and surface functionality. Scheme 2. Properties of gold nanoparticles Spherical AuNPs possess useful attributes such as size- and shape-related optoelectronic properties, 18 large surface-to-volume ratio, excellent biocompatibility, and low toxicity.
Table 1 Properties of AuNPs and their area of application. Properties Application area Redox activity Electronic devices 28 and electrochemical sensing 29 Surface-enhanced Raman scattering SERS Imaging 30 and sensing 31 Surface plasmon resonance SPR Colorimetric sensing 32 and photothermal therapy 33 Fluorescence quenching Sensor fabrication 34 and materials science Conjugation strategies for gold nanoparticles The labile capping ligands on AuNPs citrates, thiols, or other adsorbed ligands can be displaced by thiols through a place ligand exchange reaction to synthesize mixed monolayer-protected AuNPs Scheme 2A.
Scheme 3. Conjugation strategies of AuNPs through covalent and non-covalent conjugation. Applications in bionanotechnology 5. Sensing AuNPs are readily conjugated with recognition moieties such as antibodies or oligonucleotides for the detection of target biomolecules, 43 allowing in vitro detection and diagnostics applications for diseases such as cancer. Scheme 4. Therapeutics The transport of therapeutic agents to the cells by AuNPs is a critical process in biomedical treatment.
Scheme 5. Imaging The versatile optical and electronic properties of AuNPs have been employed for cell imaging using various techniques, including computed tomography CT , 78 dark-field light scattering, 79 optical coherence tomography OCT , 80 photothermal heterodyne imaging technique 81 and Raman spectroscopy.
Conclusions and Outlook AuNPs have multiple attributes that make them potent tools for the use in bionanotechnology. References 1. ACS Nano. Nano Lett. Nanoparticle Research. Nano Today.
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