Inhibiting HER3 Hyperphosphorylation in HER2-Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells.

Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+ /HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier.

Cubic Anisotropic Co- and Zn-Substituted Ferrite Nanoparticles as Multimodal Magnetic Agents.

The use of magnetic nanoparticles as theranostic agents for the detection and treatment of cancer diseases has been extensively analyzed in the last few years. In this work, cubic-shaped cobalt and zinc-doped iron oxide nanoparticles with edge lengths in the range from 28 to 94 nm are proposed as negative contrast agents for magnetic resonance imaging and to generate localized heat by magnetic hyperthermia, obtaining high values of transverse relaxation coefficients and specific adsorption rates. The applied magnetic fields presented suitable characteristics for the potential validation of the results into the clinical practice in all cases. Pure iron oxide and cobalt- and zinc-substituted ferrites have been structurally and magnetically characterized, observing magnetite as the predominant phase and weak ferrimagnetic behavior at room temperature, with saturation values even larger than those of bulk magnetite. The coercive force increased due to the incorporation of cobalt ions, while zinc substitution promotes a significant increase in saturation magnetization. After their transfer to aqueous solution, those particles showing the best properties were chosen for evaluation in in vitro cell models, exhibiting high critical cytotoxic concentrations and high internalization degrees in several cell lines. The magnetic behavior of the nanocubes after their successful cell internalization was analyzed, detecting negligible variations on their magnetic hysteresis loops and a significant decrease in the specific adsorption rate values.

Triggered RNAi Therapy Using Metal Inorganic Nanovectors.

The administration of small interfering RNA (siRNA) is a very interesting therapeutic option to treat genetic diseases such as Alzheimer's or some types of cancer, but its effective delivery still remains a challenge. Herein, Au nanorod (GNR)-based platforms functionalized with polyelectrolyte layers were developed and analyzed as potential siRNA nanocarriers. The polymeric layers were successfully assembled on the particle surfaces by means of the layer-by-layer assembly technique through the alternating deposition of oppositely charged poly(styrene)sulfonate, PSS, poly(lysine), PLL, and siRNA biopolymers, with a final hyaluronic acid layer in order to provide the nanoconstructs with a potential targeting ability as well as colloidal stability in physiological medium. Once the hybrid nanocarriers were obtained, the cargo release, their colloidal stability in physiological-relevant media, cytotoxicity, cellular internalization and uptake, and knockdown activity were studied. The present hybrid particles release the genetic material inside cells by means of a protease-assisted and/or a light-triggered release mechanism in order to control the delivery of the oligonucleotides on demand. In addition, the hybrid nanovectors were observed to be nontoxic to cells and could efficiently deliver the genetic material in the cell cytoplasms. The GNR-based nanocarriers proposed here can provide a suitable environment to load and protect a sufficient amount of the genetic material to allow an efficient and sustained knockdown gene expression for long (up to 93% for 72 h), thanks to the slow degradation of PLL, without the observation of adverse side toxic effects. It was also found that the silencing activity was enhanced with the number of siRNA layers assembled in the nanoplatforms.

A study of reproducibility of kinesiology tape applications: review, reliability and validity.

BACKGROUND: Literature addressing the mechanical properties of kinesiology tape is quite scarce. There are no studies which focus on the mechanical characteristics of kinesiology tape, its mechanical properties, nor its adherence following the ISO international standard test methods for tape elongation. METHODS: This study quantified the mechanical characteristics of 380 samples of kinesiology tape from 19 different brands and in 4 different colors using a dynamometer. Mechanical testing was controlled by UNE EN ISO 13934-1. RESULTS: Significant differences were found between tape brands in terms of grammage, maximum force tenacity, work, pre-elongation and percentage elongation (P < .001). Regarding kinesiology tape color, statistically significant differences were found between tape brands in terms of grammage, maximum force and tenacity (P < .001), work and pre-elongation (P < .05). When adherence was studied, statistically significant differences were found between tape brands in terms of maximum force and work (P < .001). CONCLUSIONS: The different kinesiology tapes presented different behaviors with regard to rupture and removal when applied to skin in dry state, wet state and after being submerged in artificial acidic sweat solution. Therefore, different kinesiology tape brands will produce different levels of strain even though the same elongation is used. Depending on the characteristics (body dimensions) and properties (skin elongation) of each subject in the sample, bandages with different elongations must be applied to achieve the same strain in all of the tapes and therefore produce the same effect. The absence of these data at this time limits the reliability of previous clinical studies, makes comparing their findings impossible and presents new challenges for research in this field.

Hybrid folic acid-conjugated gold nanorods-loaded human serum albumin nanoparticles for simultaneous photothermal and chemotherapeutic therapy.

Hybrid nanoparticles containing both structural and functional nanocomponents might result in higher success and increased quality of life for patients suffering a disease such as cancer. In this study, we combine chemotherapy of conventional drug doxorubicin (Dox) with gold nanorods (AuNR) for photothermal therapy using multifunctional human serum albumin nanoparticles (HSA NP's) fabricated via desolvation technique with high efficiency. Folic acid (FA) was conjugated to HSA NP's trough an amidation via carbodiimide reaction for a more specific nanoplataform to HeLa cancer cells. The loading efficiency of Dox into AuNR loaded-HSA NP reached up to 2 µg Dox/mg HSA. The HSA-AuNR-Dox NP experienced photothermal heating varying laser potency (1, 0.5 and 0.2 W); reaching the bulk particle solution an increment of 16, 8 and 6 °C after 10 min of near-IR laser exposure respectively. When HeLa cells were treated with this multifunctional nanoplataform containing only AuNR, cancer cells experienced 96% cell viability without irradiation and 55% cell viability after just one irradiation session. When Dox is present in the nanoplataform, viability were 60% and 24% for non-irradiated and irradiated nanoplataforms, respectively. This study demonstrates that HSA-AuNR-Dox nanoparticles are suitable systems allowing a synergic chemo and phothothermal therapy.