Hybrid Gold Nanorod-Based Nanoplatform with Chemo and Photothermal Activities for Bimodal Cancer Therapy.
Lilia Arellano-GalindoEva M VillarAlejandro VarelaValeria FigueroaJavier Fernandez-VegaAdriana CambónGerardo PrietoSilvia BarbosaPablo TaboadaPublished in: International journal of molecular sciences (2022)
Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.
Keyphrases
- cancer therapy
- cell cycle arrest
- cell death
- drug delivery
- photodynamic therapy
- pi k akt
- induced apoptosis
- drug release
- hyaluronic acid
- single cell
- gene expression
- oxidative stress
- cell therapy
- squamous cell carcinoma
- endoplasmic reticulum stress
- metabolic syndrome
- drug induced
- high throughput
- emergency department
- stem cells
- cell proliferation
- weight loss
- radiation therapy
- cardiovascular disease
- signaling pathway
- fluorescent probe
- diabetic rats
- electronic health record