PEGylated Gold Nanoparticles Conjugated to Monoclonal F19 Antibodies as Targeted Labeling Agents for Human Pancreatic Carcinoma Tissue

Eck, Wolfgang; Craig, Gary A.; Sigdel, Aruna; Ritter, Gerd; Old, Lloyd J.; Tang, Laura H.; Brennan, Murray F.; Allen, Peter J.; Mason, Michael D.

doi:10.1021/nn800429d

Cited by 250 publications

(216 citation statements)

References 62 publications

Supporting

Mentioning

206

Contrasting

Unclassified

Order By: Relevance

“…[2][3][4][5] The formation of protein conjugates allows for the stabilization of AuNPs over a broad range of pH and ionic strengths and enables the introduction of biologically active functionalities either directly (as part of the protein itself) or via further couplings with the surface-bound protein or underlying gold surface. 6,7 For example, antibodyfunctionalized AuNPs 8 and tumor necrosis factor (TNF)-conjugated AuNPs [3][4][5] have been used for targeted cancer therapeutics. 19,20 proposed using series-specific albumin in combination with a naturally occurring lung fluid surfactant dissolved in phosphate buffered saline (PBS) as a dispersion medium for nanoparticles in the context of in vivo pulmonary toxicity testing.…”

Section: Introductionmentioning

confidence: 99%

Adsorption and Conformation of Serum Albumin Protein on Gold Nanoparticles Investigated Using Dimensional Measurements and in Situ Spectroscopic Methods

et al. 2011

View full text Add to dashboard Cite

ABSTRACT:The adsorption and conformation of bovine serum albumin (BSA) on gold nanoparticles (AuNPs) were interrogated both qualitatively and quantitatively via complementary physicochemical characterization methods. Dynamic light scattering (DLS), asymmetric-flow field flow fractionation (AFFF), fluorescence spectrometry, and attenuated total reflectanceFourier transform infrared (ATR-FTIR) spectroscopy were combined to characterize BSA-AuNP conjugates under fluid conditions, while conjugates in the aerosol state were characterized by electrospray-differential mobility analysis (ES-DMA). The presence of unbound BSA molecules interferes with DLS analysis of the conjugates, particularly as the AuNP size decreases (i.e., below 30 nm in diameter). Under conditions where the γ value is high, where γ is defined as the ratio of scattering intensity by AuNPs to the scattering intensity by unbound BSA, DLS size results are consistent with results obtained after fractionation by AFFF. Additionally, the AuNP hydrodynamic size exhibits a greater proportional increase due to BSA conjugation at pH values below 2.5 compared with less acidic pH values (3.4-7.3), corresponding with the reversibly denatured (E or F form) conformation of BSA below pH 2.5. Over the pH range from 3.4 to 7.3, the hydrodynamic size of the conjugate is nearly constant, suggesting conformational stability over this range. Because of the difference in the measurement environment, a larger increase of AuNP size is observed following BSA conjugation when measured in the wet state (i.e., by DLS and AFFF) compared to the dry state (by ES-DMA). Molecular surface density for BSA is estimated based on ES-DMA and fluorescence measurements. Results from the two techniques are consistent and similar, but slightly higher for ES-DMA, with an average adsorbate density of 0.015 nm -2 . Moreover, from the change of particle size, we determine the extent of adsorption for BSA on AuNPs using DLS and ES-DMA at 21°C, which show that increasing the concentration of BSA increases the measured change in AuNP size. Using ES-DMA, we observe that the BSA surface density reaches 90% of saturation at a solution phase concentration between 10 and 30 μmol/L, which is roughly consistent with fluorescence and ATR-FTIR results. The equilibrium binding constant for BSA on AuNPs is calculated by applying the Langmuir equation, with resulting values ranging from 0.51 Â 10 6 to 1.65 Â 10 6 L/mol, suggesting a strong affinity due to bonding between the single free exterior thiol on N-form BSA (associated with a cysteine residue) and the AuNP surface. Moreover, the adsorption interaction induces a conformational change in BSA secondary structure, resulting in less R-helix content and more open structures (β-sheet, random, or expanded).

show abstract

Section: Introductionmentioning

confidence: 99%

Adsorption and Conformation of Serum Albumin Protein on Gold Nanoparticles Investigated Using Dimensional Measurements and in Situ Spectroscopic Methods

et al. 2011

View full text Add to dashboard Cite

show abstract

“…In addition, PEG is non-toxic and non-immunogenic, and has favorable pharmacokinetics and tissue distribution [18]. Modifying the surface of NPs with PEG (PEGylation) not only prevents agglomeration [19], but also renders NPs resistant to protein adsorption and enhances their biocompatibility [20]. Coating nanomaterials with PEG also increases ReticuloEndothelial System (RES) [21].…”

Section: Introductionmentioning

confidence: 99%

Effects of Toll-like Receptors 3 and 4 Induced by Titanium Dioxide Nanoparticles in DNA Damage-Detecting Sensor Cells

El-Said¹

2013

J Biosens Bioelectron

View full text Add to dashboard Cite

Live cell-based sensor reporter systems (so-called sensor cells) were employed to detect host defense systems, including DNA damage response, stimulated by nanoparticles (NPs). Our previous work established the use of DNA damage-detecting sensor cells containing the B-cell translocation gene 2(BTG2) promoter-reporter plasmid and showed that Toll-like receptors (TLRs) are involved in the cellular response and uptake of TiO 2 NPs. These results suggested that TLRs could be involved in many cellular responses. However, the effect of TLRs on DNA damage induced by TiO 2 NPs is unknown. Here we investigated the role of TLR 3 and 4 in DNA damage induced by PEG-2 NPs reduces DNA damage response compared to unmodified TiO 2 NPs. The overexpression of TLR3 reduces DNA damage mediated by both TiO 2 and PEG-TiO 2 NPs. In contrast, overexpression of TLR4 increases the DNA damage response induced by TiO 2 NPs. The results indicate that co-transfection of TRL4 expression vector affects the sensitivity of DNA damage response, but does not affect the detection limit of the DNA damage response. These finding will aid in understanding the molecular interaction mechanisms between NPs and cells.

show abstract

“…Other authors have taken a different approach to addressing the use of AuNPs in cancer biomarker detection by employing the biological applications of antibody-conjugated AuNPs in several types of cancer, such as breast cancer (Ambrosi et al, 2010;Lu et al, 2010a), pancreatic adenocarcinoma (Eck et al, 2008), cervical cancer (Rahman et al, 2005), epithelial cancer (Yang et al, 2008), liver cancer (Lan et al, 2011), prostate cancer (Lukianova-Hleb et al, 2011 Direct detection of cancer cells using colorimetric assays with AuNPs has been extensively used due to their simplicity and versatility, among which those based on LSPR. LSPR is the collective oscillation of the electrons in the conduction band, which is usually in the visible region giving rise to the strong surface plasmon resonance absorption (Daniel and Astruc, 2004).…”

Section: Gold Nanocarriers In Cancer Diagnosismentioning

confidence: 99%

Multifunctional Gold Nanocarriers for Cancer Theranostics: From Bench to Bedside and Back Again?

Conde

Tian²,

Baptista

et al. 2014

Nano-Oncologicals

View full text Add to dashboard Cite

After a quarter of century of rapid technological advances, research has revealed the complexity of cancer, a disease intimately related to the dynamic transformation of the genome. However, the full understanding of the molecular onset of this disease is still far from achieved and the search for mechanisms of treatment will follow closely.It is here that Nanotechnology enters the fray offering a wealth of tools to diagnose and treat cancer.It is indisputable that the use of gold nanocarriers has been gaining momentum as vectors for therapy and diagnostic strategies, combining the AuNPs' ease of functionalization with numerous biomolecules, high loading capacity and fast uptake by target cells. In fact, over the last decade nearly 12.000 research papers focusing on multifunctional gold nanocarriers have been published in peer-reviewed journals. Some of the described nanosystems will most likely revolutionize our understanding of biological mechanisms and push forward the clinical practice through their 2 integration in future diagnostics platforms. Nevertheless, very little gave fruitful results in order to improve a bench-to-bedside approach to translational research. On the basis of theoretical and experimental results obtained so far are we or not at the point: from bench to bedside and back again? As you will see, the answers to this question are complex, but one thing is clear: Translation into clinics is a tortuous and difficult path. Here, we provide a critical review about the available multifunctional gold nanocarriers for in vitro application and in vivo cancer targeting on nanodiagnostics and therapy.

show abstract

PEGylated Gold Nanoparticles Conjugated to Monoclonal F19 Antibodies as Targeted Labeling Agents for Human Pancreatic Carcinoma Tissue

Cited by 250 publications

References 62 publications

Adsorption and Conformation of Serum Albumin Protein on Gold Nanoparticles Investigated Using Dimensional Measurements and in Situ Spectroscopic Methods

Adsorption and Conformation of Serum Albumin Protein on Gold Nanoparticles Investigated Using Dimensional Measurements and in Situ Spectroscopic Methods

Effects of Toll-like Receptors 3 and 4 Induced by Titanium Dioxide Nanoparticles in DNA Damage-Detecting Sensor Cells

Multifunctional Gold Nanocarriers for Cancer Theranostics: From Bench to Bedside and Back Again?

Contact Info

Product

Resources

About