Gold Nanorods and Nanoprisms Mediate Different Photothermal Cell Death Mechanisms In Vitro and In Vivo.

Photothermal therapy (PTT) is an efficient method of inducing localized hyperthermia and can be achieved using gold nanoparticles as photothermal agents. However, there are many hurdles to get over before this therapy can safely reach the clinics, including nanoparticles' optimal shape and the accurate prediction of cellular responses. Here, we describe the synthesis of gold nanorods and nanoprisms with similar surface plasmon resonances in the near-infrared (NIR) and comparable photothermal conversion efficiencies and characterize the response to NIR irradiation in two biological systems, melanoma cells and the small invertebrate Hydra vulgaris. By integrating animal, cellular, and molecular biology approaches, we show a diverse outcome of nanorods and nanoprisms on the two systems, sustained by the elicitation of different pathways, from necrosis to programmed cell death mechanisms (apoptosis and necroptosis). The comparative multilevel analysis shows great accuracy of in vivo invertebrate models to predict overall responses to photothermal challenging and superior photothermal performance of nanoprisms. Understanding the molecular pathways of these responses may help develop optimized nanoheaters that, safe by design, may improve PTT efficacy for clinical purposes.

Deciphering intracellular events triggered by mild magnetic hyperthermia in vitro and in vivo.

AIM: To assess the cell response to magnetic nanoparticles under an alternating magnetic field by molecular quantification of heat responsive transcripts in two model systems. MATERIALS & METHODS: Melanoma cells and Hydra vulgaris treated with magnetic nanoparticles were subjected to an alternating magnetic field or to macroscopic heating. Effect to these treatments were assessed at animal, cellular and molecular levels. RESULTS: By comparing hsp70 expression following both treatments, thermotolerance pathways were found in both systems in absence of cell ablation or global temperature increment. CONCLUSION: Analysis of hsp70 transcriptional activation can be used as molecular thermometer to sense cells' response to magnetic hyperthermia. Similar responses were found in cells and Hydra, suggesting a general mechanism to the delivery of sublethal thermal doses.

Gold nanoprisms for photothermal cell ablation in vivo.

AIM: To develop new methodologies for selective cell ablation in a temporally and spatially precise fashion in model organisms. MATERIALS & METHODS: living polyps (Hydra vulgaris) treated with gold nanoprisms were near-infrared (NIR) irradiated and the photothermal effects evaluated at whole-animal, cellular and molecular levels. RESULTS: Nanoprisms showed good efficiency of internalization in living specimens, with no sign of toxicity; under NIR irradiation they induced cell death and the overexpression of the hsp70 gene. CONCLUSION: gold nanoprisms could be employed as efficient heat mediators in model organisms, and NIR-triggered cell ablation may represent a new advanced tool to study cell function. Solving bioethical and economical issues, invertebrates may provide alternative models bridging the gap between cell research and preclinical studies of photothermal therapy.

Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine.

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.