Identification of the Proteins Determining the Blood Circulation Time of Nanoparticles.

The therapeutic efficacy and adverse impacts of nanoparticles (NPs) are strongly dependent on their systemic circulation time. The corona proteins adsorbed on the NPs determine their plasma half-lives, and hence, it is crucial to identify the proteins shortening or extending their circulation time. In this work, the in vivo circulation time and corona composition of superparamagnetic iron oxide nanoparticles (SPIONs) with different surface charges/chemistries were analyzed over time. SPIONs with neutral and positive charges showed the longest and shortest circulation times, respectively. The most striking observation was that corona-coated NPs with similar opsonin/dysopsonin content showed different circulation times, implying these biomolecules are not the only contributing factors. Long-circulating NPs adsorb higher concentrations of osteopontin, lipoprotein lipase, coagulation factor VII, matrix Gla protein, secreted phosphoprotein 24, alpha-2-HS-glycoprotein, and apolipoprotein C-I, while short-circulating NPs adsorb higher amounts of hemoglobin. Therefore, these proteins may be considered to be determining factors governing the NP systemic circulation time.

Encapsulation of Luminescent Gold Nanoclusters into Synthetic Vesicles.

Gold nanoclusters (Au NCs) are attractive luminescent nanoprobes for biomedical applications. In vivo biosensing and bioimaging requires the delivery of the Au NCs into subcellular compartments. In this view, we explore here the possible encapsulation of ultra-small-sized red and blue emitting Au NCs into liposomes of various sizes and chemical compositions. Different methods were investigated to prepare vesicles containing Au NCs in their lumen. The efficiency of the process was correlated to the structural and morphological aspect of the Au NCs' encapsulating vesicles thanks to complementary analyses by SAXS, cryo-TEM, and confocal microscopy techniques. Cell-like-sized vesicles (GUVs) encapsulating red or blue Au NCs were successfully obtained by an innovative method using emulsion phase transfer. Furthermore, exosome-like-sized vesicles (LUVs) containing Au NCs were obtained with an encapsulation yield of 40%, as estimated from ICP-MS.

Luminescent Gold Nanoclusters Interacting with Synthetic and Biological Vesicles.

According to their high electron density and ultrasmall size, gold nanoclusters (AuNCs) have unique luminescence and photoelectrochemical properties that make them very attractive for various biomedical fields. These applications require a clear understanding of their interaction with biological membranes. Here we demonstrate the ability of the AuNCs as markers for lipidic bilayer structures such as synthetic liposomes and biological extracellular vesicles (EVs). The AuNCs can selectively interact with liposomes or EVs through an attractive electrostatic interaction as demonstrated by zetametry and fluorescence microscopy. According to the ratio of nanoclusters to vesicles, the lipidic membranes can be fluorescently labeled without altering their thickness until charge reversion, the AuNCs being located at the level of the phosphate headgroups. In presence of an excess of AuNCs, the vesicles tend to adhere and aggregate. The strong adsorption of AuNCs results in the formation of a lamellar phase as demonstrated by cryo-transmission electron microscopy and small-angle X-ray scattering techniques.

In vivo protein corona on nanoparticles: does the control of all material parameters orient the biological behavior?

Nanomaterials have a huge potential in research fields from nanomedicine to medical devices. However, surface modifications of nanoparticles (NPs) and thus of their physicochemical properties failed to predict their biological behavior. This requires investigating the "missing link" at the nano-bio interface. The protein corona (PC), the set of proteins binding to the NPs surface, plays a critical role in particle recognition by the innate immune system. Still, in vitro incubation offers a limited understanding of biological interactions and fails to explain the in vivo fate. To date, several reports explained the impact of PC in vitro but its applications in the clinical field have been very limited. Furthermore, PC is often considered as a biological barrier reducing the targeting efficiency of nano vehicles. But the protein binding can actually be controlled by altering PC both in vitro and in vivo. Analyzing PC in vivo could accordingly provide a deep understanding of its biological effect and speed up the transfer to clinical applications. This review demonstrates the need for clarifications on the effect of PC in vivo and the control of its behavior by changing its physicochemical properties. It unfolds the recent in vivo developments to understand mechanisms and challenges at the nano-bio interface. Finally, it reports recent advances in the in vivo PC to overcome and control the limitations of the in vitro PC by employing PC as a boosting resource to prolong the NPs half-life, to improve their formulations and thereby to increase its use for biomedical applications.