Monosaccharides <i>versus</i> PEG-Functionalized NPs: Influence in the Cellular Uptake

Magnetic nanoparticles (NPs) hold great promise for biomedical applications. The core composition and small size of these particles produce superparamagnetic behavior, thus facilitating their use in magnetic resonance imaging and magnetically induced therapeutic hyperthermia. However, the development and control of safe <i>in vivo</i> applications for NPs call for the study of cell–NP interactions and cell viability. Furthermore, as for most biotechnological applications, it is desirable to prevent unspecific cell internalization of these particles. It is also crucial to understand how the surface composition of the NPs affects their internalization capacity. Here, through accurate control over unspecific protein adsorption, size distribution, grafting density, and an extensive physicochemical characterization, we correlated the cytotoxicity and cellular uptake mechanism of 6 nm magnetic NPs coated with several types and various densities of biomolecules, such as glucose, galactose, and poly(ethylene glycol). We found that the density of the grafted molecule was crucial to prevent unspecific uptake of NPs by Vero cells. Surprisingly, the glucose-coated NPs described here showed cellular uptake as a result of lipid raft instead of clathrin-mediated cellular internalization. Moreover, these glucose-functionalized NPs could be one of the first examples of NPs being endocytosed by caveolae that finally end up in the lysosomes. These results reinforce the use of simple carbohydrates as an alternative to PEG molecules for NPs functionalization when cellular uptake is required

Dissecting the Molecular Mechanism of Apoptosis during Photothermal Therapy Using Gold Nanoprisms

The photothermal response of plasmonic nanomaterials can be exploited for a number of biomedical applications in diagnostics (biosensing and optoacoustic imaging) and therapy (drug delivery and photothermal therapy). The most common cellular response to photothermal cancer treatment (ablation of solid tumors) using plasmonic nanomaterials is necrosis, a process that releases intracellular constituents into the extracellular milieu producing detrimental inflammatory responses. Here we report the use of laser-induced photothermal therapy employing gold nanoprisms (NPRs) to specifically induce apoptosis in mouse embryonic fibroblast cells transformed with the SV40 virus. Laser-irradiated “hot” NPRs activate the intrinsic/mitochondrial pathway of apoptosis (programmed cell death), which is mediated by the nuclear-encoded proteins Bak and Bax through the activation of the BH3-only protein Bid. We confirm that an apoptosis mechanism is responsible by showing how the NPR-mediated cell death is dependent on the presence of caspase-9 and caspase-3 proteins. The ability to selectively induce apoptotic cell death and to understand the subsequent mechanisms provides the foundations to predict and optimize NP-based photothermal therapy to treat cancer patients suffering from chemo- and radioresistance

Effect of Surface Chemistry and Associated Protein Corona on the Long-Term Biodegradation of Iron Oxide Nanoparticles In Vivo

The protein corona formed on the surface of a nanoparticle in a biological medium determines its behavior in vivo. Herein, iron oxide nanoparticles containing the same core and shell, but bearing two different surface coatings, either glucose or poly­(ethylene glycol), were evaluated. The nanoparticles’ protein adsorption, in vitro degradation, and in vivo biodistribution and biotransformation over four months were investigated. Although both types of nanoparticles bound similar amounts of proteins in vitro, the differences in the protein corona composition correlated to the nanoparticles biodistribution in vivo. Interestingly, in vitro degradation studies demonstrated faster degradation for nanoparticles functionalized with glucose, whereas the in vivo results were opposite with accelerated biodegradation and clearance of the nanoparticles functionalized with poly­(ethylene glycol). Therefore, the variation in the degradation rate observed in vivo could be related not only to the molecules attached to the surface, but also with the associated protein corona, as the key role of the adsorbed proteins on the magnetic core degradation has been demonstrated in vitro