RESUMEN
Temperature-trigger chemotherapy is one of the state-of-the-art anti-tumoral strategies in nanomedicine. However, this strategy is in close relationship with the effect of the temperature in the tumor tissue. With high temperatures, the ablation of the tumor tissue can hinder a correct chemotherapy approximation. On the other hand, with moderate temperatures a negative vascularization that promotes the tumor growing is produced and competes with the chemotherapeutic effects. We have constructed one nanogel system composed of a thermoresponsive polymer cross-linked by plasmonic gold nanoparticles (AuNPs) for temperature-trigger chemotherapy. Doxorubicin loaded in the porous interior of the nanogel is released when the thermoresponsive network of the nanogel collapses due to the heat generated by the AuNPs upon near infra-red light irradiation. The hybrid nanogel system has been tested in vitro and in vivo, where it was observed that the temperatures reached in the in vivo NIR irradiation have an undesired effect on the inhibition of the tumor growth while the drug loaded systems considerably reduced the tumor sizes. This study shows the importance of design in temperature triggered antitumoral systems, where lower temperatures usually reached in practical situations due to light attenuation produced by the tissue can be positively utilized for enhancing the antitumoral effect of loaded drugs in the system.
Asunto(s)
Nanopartículas del Metal , Neoplasias , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Oro , Humanos , Nanopartículas del Metal/uso terapéutico , Nanogeles , Neoplasias/tratamiento farmacológicoRESUMEN
Magnetoplasmonic nanomaterials, which combine light and magnetic field responsiveness in an advantageous manner, are attractive candidates for bio-nanoapplications. However, the synthetic access to such hybrid particles has been limited by the incompatibility of the iron- and gold-based lattices. In this work, we provide the first insights into a new synthetic strategy for developing magnetoplasmonic anisotropic nanocomposites with prominent phototransducing properties. In our approach, magnetic nanocubes based on an alloy of iron oxide, zinc, and silver were constructed. In a key second stage, the galvanic replacement of silver with gold atoms yielded satellite-like magnetoplasmonic anisotropic structures. Superior magnetic and photoconverting properties were observed for the novel magnetoplasmonic nanocomposites when compared with the pure parent structures. Moreover, the synergy between the magnetic and optical stimuli was examined, showing shape-dependent contributions in the magnetization experiments. More importantly, an excellent cell ablation capability upon laser irradiation was observed for the magnetoplasmonic nanocomposites compared to the pure magnetic or plasmonic controls. Further demonstration of these novel theragnostic agents as MRI contrast agents is also reported even during the light-irradiation event. Thus, the described particles showed promising properties for bioapplications emerging from the novel synthetic methodology.
RESUMEN
With increasing importance of gold nanoparticles (AuNPs) in the medical field, the understanding of their interactions in biological environments is essential. It is known that the exposure to biological fluids of particles in the nanometric range leads to accumulation of proteins on the particle surface proximity, generating the so-called protein corona. This fact can completely change the properties of AuNPs, thus drastically influencing the characteristics and intended purpose of the particles. Therefore, deep insight on the formation and composition of this protein corona is of extreme importance. Between the different factors that can alter the corona formation, our study focuses on the influence of the shape and particle surface charge. In detail, four different shapes of nanometrical scale (spheres, rods, stars and cages) of comparable size were used, all of them stabilized with three different heterofunctionalized poly(ethylene glycol) thiol (R-PEG-SH) linkers (R = OCH3, COOH or NH2) to check the effect of charge as well. After incubation with human serum, abundant proteins were identified via liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC ESI MS/MS) and compared in terms of their relative abundance. On the basis of statistical evaluations, the shape of our AuNPs showed a greater influence than the surface charge. Especially, cage-shaped AuNPs showed a lower amount of total corona proteins. This shape showed differences in the abundances of individual proteins like albumin, vitronectin and members of the complement system. These results indicate that nanocages could present an improved biocompatibility compared with the other shapes due to the high curvature areas and dense ligation on the flat surfaces that could hinder opsonisation and fast removal by the immune system.
Asunto(s)
Nanopartículas del Metal , Corona de Proteínas , Oro , Humanos , Tamaño de la Partícula , Polietilenglicoles , Espectrometría de Masas en TándemRESUMEN
Biomimetic magnetite nanoparticles (BMNPs) synthesized in the presence of MamC, a magnetosome-associated protein from Magnetoccus marinus MC-1, have gained interest for biomedical applications because of their unique magnetic properties. However, their behavior in biological systems, like their interaction with proteins, still has to be evaluated prior to their use in clinics. In this study, doxorubicin (DOXO) as a model drug was adsorbed onto BMNPs to form nanoassemblies. These were incubated with human plasma to trigger protein corona (PC) formation. Proteins from the human plasma stably attached to either BMNPs or DOXO-BMNP nanoassemblies. In particular, fibrinogen was detected as the main component in the PC of DOXO-BMNPs that potentially provides advantages, e.g. protecting the particles from phagocytosis, thus prolonging their circulation time. Adsorption of PC to the BMNPs did not alter their magnetic properties but improved their colloidal stability, thus reducing their toxicity in human macrophages. In addition, PC formation enhanced cellular internalization and did not interfere with DOXO activity. Overall, our data indicate that the adsorption of PC onto DOXO-BMNPs in biological environment even increases their efficiency as drug carrier systems.