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1.
Cells ; 11(22)2022 11 17.
Article in English | MEDLINE | ID: mdl-36429072

ABSTRACT

Applications of nanoparticles (NPs) in the life sciences require control over their properties in protein-rich biological fluids, as an NP quickly acquires a layer of proteins on the surface, forming the so-called "protein corona" (PC). Understanding the composition and kinetics of the PC at the molecular level is of considerable importance for controlling NP interaction with cells. Here, we present a systematic study of hard PC formation on the surface of upconversion nanoparticles (UCNPs) coated with positively-charged polyethyleneimine (PEI) and negatively-charged poly (acrylic acid) (PAA) polymers in serum-supplemented cell culture medium. The rationale behind the choice of UCNP is two-fold: UCNP represents a convenient model of NP with a size ranging from 5 nm to >200 nm, while the unique photoluminescent properties of UCNP enable direct observation of the PC formation, which may provide new insight into this complex process. The non-linear optical properties of UCNP were utilised for direct observation of PC formation by means of fluorescence correlation spectroscopy. Our findings indicated that the charge of the surface polymer coating was the key factor for the formation of PC on UCNPs, with an ensuing effect on the NP-cell interactions.


Subject(s)
Nanoparticles , Protein Corona , Polymers , Cell Communication , Polyethyleneimine
2.
Molecules ; 25(18)2020 Sep 19.
Article in English | MEDLINE | ID: mdl-32961731

ABSTRACT

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.


Subject(s)
Metal Nanoparticles/chemistry , Theranostic Nanomedicine , Animals , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Female , Fluorescent Dyes/chemistry , Fluorides/chemistry , Humans , Metal Nanoparticles/therapeutic use , Metal Nanoparticles/toxicity , Mice , Mice, Nude , Polyethylene Glycols/chemistry , Receptor, ErbB-2/metabolism , Thulium/chemistry , Transplantation, Heterologous , Ytterbium/chemistry , Yttrium/chemistry
3.
Toxicol Sci ; 170(1): 123-132, 2019 07 01.
Article in English | MEDLINE | ID: mdl-30985900

ABSTRACT

Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. Upconversion nanoparticle applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb, Er, Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin 9_29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, noncytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery.


Subject(s)
Mammary Neoplasms, Experimental/diagnostic imaging , Nanoparticles/chemistry , Polymers/chemistry , Whole Body Imaging/methods , Animals , CHO Cells , Cell Line, Tumor , Cricetulus , Drug Evaluation, Preclinical , Erbium/chemistry , Escherichia coli/genetics , Fluorides/chemistry , Humans , Luminescent Measurements , Nanoparticles/metabolism , Nanoparticles/toxicity , Polymers/pharmacokinetics , Polymers/toxicity , Receptor, ErbB-2/genetics , Surface Properties , Thulium/chemistry , Tissue Distribution , Yttrium/chemistry
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