Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach

Coelho, Sílvia Castro; Rangel, Maria; Pereira, Maria do Carmo; Coelho, Manuel A. N.; Ivanova, Galya

doi:10.1039/c5cp02717a

Cited by 31 publications

(17 citation statements)

References 48 publications

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“…In general, non-covalent methods (electrostatic adsorption or hydrophobic interactions) are reported as simple and effective approaches for drugs bioconjugation, in the presence of functionalized AuNPs. Thanks to the relatively weak affinity of the gold surface and/or the presence of thiol stabilizing layer, several drugs can be adsorbed, with a general retention of the therapeutic activities [62][63][64].…”

Section: Resultsmentioning

confidence: 99%

Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

Bessar

Venditti

Benassi

et al. 2016

Colloids and Surfaces B: Biointerfaces

116

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a b s t r a c tGold nanoparticles (AuNPs) represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. Even if systemic, methotrexate still plays an important role in psoriasis treatment: its topical use shows insufficient percutaneus penetration owing to limited passive diffusion, high molecular weight and dissociation at physiological pH. The aim of our study was to design a new drug delivery nanocarrier for Methotrexate and to improve its solubility, stability and biodistribution. AuNPs were on purpose prepared with a hydrophilic stabilizing layer, in order to improve the colloidal stability in water. Watersoluble gold nanoparticles functionalized by sodium 3-mercapto-1-propansulfonate (Au-3MPS) were prepared and loaded with methotrexate (MTX). The loading efficiency of MTX on Au-3MPS was assessed in the range 70-80%, with a fast release (80% in one hour). The release was studied up to 24 h reaching the value of 95%. The Au-3MPS@MTX conjugate was fully characterized by spectroscopic techniques (UV-vis, FTIR) and DLS. Preliminary toxicity tests in the presence of keratinocytes monolayers allowed to assess that the used Au-3MPS are not toxic. The conjugate was then topically used on C57BL/6 mouse normal skin in order to trace the absorption behavior. STEM images clearly revealed the distribution of gold nanoparticles inside the cells. In vitro studies showed that Methotrexate conjugated with Au-3MPS is much more efficient than Methotrexate alone. Moreover, DL50, based on MTT analysis, is 20 folds reduced at 48 h, by the presence of nanoparticles conjugation. UV-vis spectra for in vivo tracing of the conjugate on bare mouse skin after 24 h of application, show increased delivery of Methotrexate in the epidermis and dermis using Au-3MPS@MTX conjugate, compared to MTX alone. Moreover we observed absence of the Au-3MPS in the dermis and in the epidermis, suggesting that these layers of the skin do not retain the nanoparticles. Based on our data, we found that the novel Au-3MPS@MTX conjugate is an effective non-toxic carrier for the satisfactory percutaneous absorption of Methotrexate and could help in possible topical treatment of psoriasis.

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Section: Resultsmentioning

confidence: 99%

Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

Bessar

Venditti

Benassi

et al. 2016

Colloids and Surfaces B: Biointerfaces

116

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“…1 Their characteristics in aqueous solutions have been investigated in both in vitro/vivo 2-12 and in silico 13-21 experiments. AuNPs interact with, for example, amyloids, 22 viruses, 23 bacteria, 24 proteins, 25-26 and DNA.…”

Section: Introductionmentioning

confidence: 99%

Aspheric Solute Ions Modulate Gold Nanoparticle Interactions in an Aqueous Solution: An Optimal Way To Reversibly Concentrate Functionalized Nanoparticles

et al. 2015

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Nanometer-sized gold particles (AuNPs) are of peculiar interest because their behaviors in an aqueous solution are sensitive to changes in environmental factors including the size and shape of the solute ions. In order to determine these important characteristics, we performed all-atom molecular dynamics simulations on the icosahedral Au144 nanoparticles each coated with a homogeneous set of 60 thiolates (4-mercapto-benzoate, pMBA) in eight aqueous solutions having ions of varying sizes and shapes (Na+, K+, tetramethylamonium cation TMA+, trisamonium cation TRS+, Cl−, and OH−). For each solution, we computed the reversible work (potential of mean of force) to bring two nanoparticles together as a function of their separation distance. We found that the behavior of pMBA protected Au144 nanoparticles can be readily modulated by tuning their aqueous environmental factors (pH and solute ion combinations). We examined the atomistic details on how the sizes and shapes of solute ions quantitatively factor in the definitive characteristics of nanoparticle-environment and nanoparticle-nanoparticle interactions. We predict that tuning the concentrations of non-spherical composite ions such as TRS+ in an aqueous solution of AuNPs be an effective means to modulate the aggregation propensity desired in biomedical and other applications of small charged nanoparticles.

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“…Charge, surface functionalization, stability and size of AuNPs are important factors for the cellular uptake process [168][169][170]. Relatively easy surface modification chemistry through thiol linkages provides large reactive surface area and great ability to carry high drug doses [143,165,171,172]. It is being debated which mechanism is suitable for efficient NP uptake by cells.…”

Section: Metal-based Nanoparticlesmentioning

confidence: 99%

Supramolecular nanoscale assemblies for cancer diagnosis and therapy

Coelho

Pereira

Juzeniene

et al. 2015

Journal of Controlled Release

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Nanocarriers based on polymers, metals and lipids have been extensively developed for cancer therapy and diagnosis due to their ability to enhance drug accumulation in cancer cells and decrease undesired drug toxicity in healthy tissues. Overcoming multidrug resistance by designing proper drug nanocarriers will improve outcome of existing oncologic treatments such as chemotherapy or radiotherapy. In this article the relation between physicochemical properties and capacity of a nanosystem to deliver therapeutic agents into pathological sites is discussed. Most promising examples of drug delivery systems are reviewed, and, in particular, the design of a carbohydrate based matrix with entrapped gold nanoparticles is highlighted.

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Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach

Cited by 31 publications

References 48 publications

Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

Aspheric Solute Ions Modulate Gold Nanoparticle Interactions in an Aqueous Solution: An Optimal Way To Reversibly Concentrate Functionalized Nanoparticles

Supramolecular nanoscale assemblies for cancer diagnosis and therapy

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