Controlled nanotherapies using magneto-plasmonic nanodomes
- Autores: Zhi Li
- Directores de la Tesis: Josep Nogués i Sanmiguel (dir. tes.), Borja Sepúlveda Martínez (dir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2019
- Idioma: español
- Tribunal Calificador de la Tesis: Anna Roig Serra (presid.), Jordi Hernando Campos (secret.), Ibane Abasolo Olaortua (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencia de Materiales por la Universidad Autónoma de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
With the aim of improving the concentration of the therapeutic agents inside tumours and maximizing their therapeutic effects, this Thesis focused on developing novel versatile magneto-plasmonic nanodomes (i.e. dielectric nanoparticles with plasmonic and ferromagnetic semi-shells) externally actuated and controlled by light and magnetic fields for efficient nanotherapy activation, amplification and control.
The innovative combination of bottom-up and top-down fabrication processes have enabled us: i) merging nanomaterials that could be hardly combined by chemical synthesis, ii) fine tuning the magnetic and optical properties, iii) achieving simple functionalization and direct dispersion in water solutions, and iv) keeping low cost and scalability.
Firstly, we developed Fe/Au nanodomes with fluorescent cores for magnetically amplified photothermal therapies and multimodal imaging. The variation of the Fe and Au layers thickness enabled attaining colloidally stable single domain or vortex ferromagnetic nanoparticles with widely tunable optical properties. Thick Fe layers provided strongly supressed scattering and high optical absorption in the near infrared, which were key to demonstrate high photothermal conversion efficiencies (ca. 65%). The capacity to magnetically concentrate the nanodomes at the illuminated region enhanced even further the local heating efficiency. The Fe/Au semi-shell and the fluorescent polymer core provided intense contrasts in T2 nuclear magnetic resonance, X-ray absorption, and fluorescence. The in vitro results showed low cytotoxicity and magnetically enhanced photothermal effects for cancer cell eradication, which highlighted the biomedical potential.
To gain control on the photothermal effects, in the second part we developed a novel simultaneous nano-heating/thermometry concept, based on the efficient magnetic rotation of highly anisotropic magneto-plasmonic nanodomes. By analyzing the nanodomes rotation as a function of the magnetic frequency, we quantified and monitored the viscosity reduction in the fluid surrounding the optically heated nanodomes, as novel nanothermometry concept. This nanothermometers showed a low detection limit of 0.05ºC, independence on their concentration, and much simpler and cost-effective detection setup than luminescent nanothermometers. The capacity to integrate heating and thermometry in a single nanostructure and using the same laser for heating and detecting were relevant advantages that could be demonstrated even in highly concentrated cell dispersions.
The final goal of the Thesis was maximizing the biomedical potential of the nanodomes for cancer nanotherapies by developing fully biodegradable drug loaded PLGA@Fe/SiO2 magnetoplasmonic nanocapsules to achieve: i) improved biodegradability, ii) reinforced magnetic actuation, iii) high photothermal conversion efficiency in both near-infrared biological windows (63-67%), iv) higher T2 contrast in nuclear magnetic resonance, and v) integrated nanothermometry and biosensing. The unloaded nanocapsules showed very low toxicity in vitro in long-term cell cultures, and in vivo in mice. The high T2 contrast was exploited to monitor the in vivo biodistribution of the nanocapsules after intravenous injection, which showed accumulation in the liver 1h after the injection, and almost total recovery after 96h. These preliminary results are encouraging for their application in multi-active local therapies.
In conclusion, we have shown how a hybrid nanofabrication strategy could exploited to develop nanostructures with strong ferromagnetic and plasmonic properties enabling external control and non-invasive visualization. The in vitro and preliminary in vivo results encourage further technological development of this novel nanotechnology for clinical applications.
