Controlled Formation of a Protein Corona Composed of Denatured BSA on Upconversion Nanoparticles Improves Their Colloidal Stability.

In the natural fluidic environment of a biological system, nanoparticles swiftly adsorb plasma proteins on their surface forming a "protein corona", which profoundly and often adversely affects their residence in the systemic circulation in vivo and their interaction with cells in vitro. It has been recognized that preformation of a protein corona under controlled conditions ameliorates the protein corona effects, including colloidal stability in serum solutions. We report on the investigation of the stabilizing effects of a denatured bovine serum albumin (dBSA) protein corona formed on the surface of upconversion nanoparticles (UCNPs). UCNPs were chosen as a nanoparticle model due to their unique photoluminescent properties suitable for background-free biological imaging and sensing. UCNP surface was modified with nitrosonium tetrafluoroborate (NOBF4) to render it hydrophilic. UCNP-NOBF4 nanoparticles were incubated in dBSA solution to form a dBSA corona followed up by lyophilization. As produced dBSA-UCNP-NOBF4 demonstrated high photoluminescence brightness, sustained colloidal stability after long-term storage and the reduced level of serum protein surface adsorption. These results show promise of dBSA-based nanoparticle pretreatment to improve the amiability to biological environments towards theranostic applications.

UCNP-based Photoluminescent Nanomedicines for Targeted Imaging and Theranostics of Cancer.

Theranostic approach is currently among the fastest growing trends in cancer treatment. It implies the creation of multifunctional agents for simultaneous precise diagnosis and targeted impact on tumor cells. A new type of theranostic complexes was created based on NaYF4: Yb,Tm upconversion nanoparticles coated with polyethylene glycol and functionalized with the HER2-specific recombinant targeted toxin DARPin-LoPE. The obtained agents bind to HER2-overexpressing human breast adenocarcinoma cells and demonstrate selective cytotoxicity against this type of cancer cells. Using fluorescent human breast adenocarcinoma xenograft models, the possibility of intravital visualization of the UCNP-based complexes biodistribution and accumulation in tumor was demonstrated.