One low-dose exposure of gold nanoparticles induces long-term changes in human cells

Falagan-Lotsch, Priscila; Grzincic, Elissa M.; Murphy, Catherine J.

doi:10.1073/pnas.1616400113

Cited by 138 publications

(147 citation statements)

References 50 publications

(61 reference statements)

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“…However it was recently shown that cells exposed to low doses of various gold nanoparticles with 'biocompatible' surfactants induce genetic changes over a long period of time [347]. This particularly resulted in the upregulation of genes associated with oxidative stress and apoptosis (amongst others) for a single (non-chronic) dose, which is the typical approach for SERS measurements.…”

Section: Challengesmentioning

confidence: 99%

“…Whilst the phototoxicity directly from the excitation source will be low, the localized hot-spot intensity is necessarily large, which could induce a variety of unwanted/damaging reactions in a complex cellular environment over time. Despite the recent in vivo studies using mouse models, it will still be difficult to envisage approval for clinical applications of SERS on humans in the near-future without (SERS-specific) long-term studies, in a similar manner to Falagan et al [347]. It is therefore more likely to see ex vivo and solution-based SERS techniques achieving success in medical applications.…”

Section: Challengesmentioning

confidence: 99%

See 1 more Smart Citation

Raman spectroscopy: techniques and applications in the life sciences

Shipp¹,

Sinjab²,

Notingher³

2017

Adv. Opt. Photon.

270

189

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Raman spectroscopy is an increasingly popular technique in many areas including biology and medicine.It is based on Raman scattering, a phenomenon in which incident photons lose or gain energy via interactions with vibrating molecules in a sample. These energy shifts can be used to obtain information regarding molecular composition of the sample with very high accuracy. Applications of Raman spectroscopy in the life sciences have included quantification of biomolecules, hyperspectral molecular imaging of cells and tissue, medical diagnosis, and others. This review briefly presents the physical origin of Raman scattering explaining the key classical and quantum mechanical concepts. Variations of the Raman effect will also be considered, including resonance, coherent, and enhanced Raman scattering. We discuss the molecular origins of prominent bands often found in the Raman spectra of biological samples. Finally, we examine several variations of Raman spectroscopy techniques in practice, looking at their applications, strengths, and challenges. This review is intended to be a starting resource for scientists new to Raman spectroscopy, providing theoretical background and practical examples as the foundation for further study and exploration.

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Section: Challengesmentioning

confidence: 99%

Section: Challengesmentioning

confidence: 99%

Raman spectroscopy: techniques and applications in the life sciences

Shipp¹,

Sinjab²,

Notingher³

2017

Adv. Opt. Photon.

270

189

View full text Add to dashboard Cite

show abstract

“…Moreover, these changes surprisingly lasted over 20 weeks. 39 Therefore, we predict the persistent accumulation of Au-NPs in the body organs could present similar toxicological responses. We emphasize that exploring the cytotoxicity of Au-NPs in extended long-term studies rather than solely investigating their acute short-term responses will not only elucidate more information about their safety profile, but also help to design safer Au-NPs for nanomedicine.…”

Section: Gold and Silver Npsmentioning

confidence: 88%

“…In addition, degradation of Au-NPs could result in formation of smaller particles that are known to be toxic, as previously mentioned. Falagan-Lotsch et al 39 explored the long-term effect of exposing wellcharacterized Au-NPs to human dermal fibroblasts in vitro and found that even a single exposure of a subcytotoxic dose of Au-NPs could change the expression of genes that are associated with oxidative stress and inflammation. Moreover, these changes surprisingly lasted over 20 weeks.…”

Section: Gold and Silver Npsmentioning

confidence: 99%

Facilitating Translational Nanomedicine via Predictive Safety Assessment

et al. 2017

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Extensive research on engineered nanomaterials (ENMs) has led to the development of numerous nano-based formulations for theranostic purposes. Although some nano-based drug delivery systems already exist on the market, growing numbers of newly designed ENMs exhibit improved physicochemical properties and are being assessed in preclinical stages. While these ENMs are designed to improve the efficacy of current nanobased therapeutic or imaging systems, it is necessary to thoroughly determine their safety profiles for successful clinical applications. As such, our aim in this mini-review is to discuss the current knowledge on predictive safety and structure-activity relationship (SAR) analysis of major ENMs at the developing stage, as well as the necessity of additional long-term toxicological analysis that would help to facilitate their transition into clinical practices. We focus on how the interaction of these nanomaterials with cells would trigger signaling pathways as molecular initiating events that lead to adverse outcomes. These mechanistic understandings would help to design safer ENMs with improved therapeutic efficacy in clinical settings.During the past decades, engineered nanomaterials (ENMs) have been widely used in biomedical applications, such as nanomedicine, bioimaging, and tissue engineering, because of their unique biophysicochemical properties.1,2 With regard to nanomedicine applications, ENMs could be formulated as drug carriers that deliver the therapeutic reagents within the human body and increase their bioavailability and blood circulation half-life.2 Moreover, these nanocarriers could be functionalized to deliver the drug specifically to the desired target tissues (e.g., tumors) and release the payload sustainably over long periods, thereby eliminating the necessity of multiple drug administration and reducing its cytotoxic side effects toward healthy cells.2 In addition to their implementation in drug delivery, ENMs could be used for diagnostic and imaging purposes that would help to monitor the disease and administer the treatment more accurately. 2Past research in nanomedicine has led to the design of various nanomaterial-based therapeutic and diagnostic systems that are being investigated in experimental stages (e.g., in vitro and in vivo) and clinical trials or are commercially available to the corresponding patients (Table 1). Most commercialized nanomaterial-based therapeutic reagents use lipids, proteins, and polymers that could self-assemble and biodegrade with few side effects.3 Because of high biocompatibility of lipids, several commercial liposome-drug formulations have been developed, mostly relying on polyethylene glycol (PEG)-conjugated lipids, such as DOXIL, AmBisome, Epaxal, and Inflexal V, and are under clinical trials focusing on various types of disease treatments. 4,5 Polymer-based nanoparticles (NPs) also present low toxicity, but their surface functionalization may affect their safety. The most commonly used materials include PEG, ploy(lactic-co-glycolic) acid (PLGA...

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“…The toxicity of NPs has consequently been studied extensively and has been the subject of detailed reviews. [61][62][63][64][65] Briefly, the toxicity and biocompatibility of NPs is largely dependent on their size, shape, charge and surface chemistry, [66][67][68][69] as well as other factors such as their propensity to aggregate. 70 Each of these properties must be carefully considered when designing nanosensors for in vivo applications and toxicological effects must be assessed when fabricating or altering probes for bioanalysis.…”

mentioning

confidence: 99%

Surface-enhanced Raman spectroscopy for in vivo biosensing

et al. 2017

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| Surface enhanced Raman scattering (SERS) is of interest for biomedical analysis and imaging due to its sensitivity, specificity and multiplexing capabilities. The successful application of SERS for in vivo biosensing necessitates probes to be biocompatible and procedures to be minimally invasive, challenges that have respectively been met by the design of nanoprobes and instrumentation. This Review presents recent developments in these areas, describing case studies in which sensors have been implemented, as well as outlining shortcomings that have to be addressed before SERS sees clinical use.In 1928, C. V. Raman first reported the scattering phenomenon that now bears his name.1,2 Raman scattering has since become a powerful analytical technique, including for biomedical applications, 3 where label-free and objective tissue diagnostics 4-6 ex vivo and in vivo, as well as drug-cell interaction studies in vitro have been conducted. [7][8][9] The majority of incident photons experience elastic (Rayleigh) scattering, with only about 1 in 10 7 photons undergoing inelastic (Raman) scattering. 10 In 1974, Fleischmann and co-workers described a phenomenon that would later become known as surface enhanced Raman scattering (SERS) 11 . They observed a large enhancement in inelastic scattering from pyridine when the analyte was adsorbed onto a Ag electrode, an effect that had previously been mentioned by the team of A. J. McQuillan in 1973, 12 with Van Duyne later attributing the signal enhancement to the roughened metal surface via the physical phenomenon he coined SERS.13 Unlike conventional Raman spectroscopy, SERS analyses require samples to be labelled, a disadvantage offset by the large intensity enhancement that makes SERS an important analytical tool with high sensitivity and low detection limits.14,15 The exact mechanism of SERS is not fully understood but an electromagnetic enhancement factor plays the major role 16 , whereby free electrons in a metal nanoparticle (NP) encounter applied radiation whose electromagnetic field varies at a frequency matching the oscillation frequency of electrons in the NPs. Such plasmon resonance at the NP surface arises from an intense electric field, which intensifies Raman modes arising from molecules near or attached to the NP surface. The Raman signals can also be enhanced due to the formation of chargetransfer complexes between the roughened metal surface and molecules bound to it. We now leave our discussion of the SERS mechanism, but refer readers interested in these fundamental principles to some comprehensive articles on the subject. [17][18][19] Well-known selection rules allow for one to predict if a given vibrational mode is infrared-and/or Raman-active. Indeed, by considering the magnitude of the change in dipole moment or polarizability associated with a vibration, one can rationalize infrared or Raman data, respectively. Compared to Raman spectroscopy, SERS involves analyte molecules interacting with a roughened metal substrate, such that the symmetry ...

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One low-dose exposure of gold nanoparticles induces long-term changes in human cells

Cited by 138 publications

References 50 publications

Raman spectroscopy: techniques and applications in the life sciences

Raman spectroscopy: techniques and applications in the life sciences

Facilitating Translational Nanomedicine via Predictive Safety Assessment

Surface-enhanced Raman spectroscopy for in vivo biosensing

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