title: Implications of protein corona on physico-chemical and biological properties of magnetic nanoparticles.
abstract: Interaction of serum proteins and nanoparticles leads to a nanoparticle-protein complex formation that defines the rational strategy for a clinically relevant formulation for drug delivery, hyperthermia, and magnetic resonance imaging (MRI) applications in cancer nanomedicine. Given this perspective, we have examined the pattern of human serum protein corona formation with our recently engineered magnetic nanoparticles (MNPs). The alteration in particle size, zeta potential, hemotoxicity, cellular uptake/cancer cells targeting potential, and MRI properties of the MNPs after formation of human serum (HS) protein corona were studied. Our results indicated no significant change in particle size of our MNPs upon incubation with 0.5-50 wt/v% human serum, while zeta potential of MNPs turned negative due to human serum adsorption. When incubated with an increased serum and particle concentration, apolipoprotein E was adsorbed on the surface of MNPs apart from serum albumin and transferrin. However, there was no significant primary or secondary structural alterations observed in serum proteins through Fourier transform infrared spectroscopy, X-ray diffraction, and circular dichroism. Hemolysis assay suggests almost no hemolysis at the tested concentrations (up to 1 mg/mL) for MNPs compared to the sodium dodecyl sulfate (positive control). Additionally, improved internalization and uptake of MNPs by C4-2B and Panc-1 cancer cells were observed upon incubation with human serum (HS). After serum protein adsorption to the surface of MNPs, the close vicinity within T1 (∼1.33-1.73 s) and T2 (∼12.35-13.43 ms) relaxation times suggest our MNPs retained inherent MRI potential even after biomolecular protein adsorption. All these superior clinical parameters potentially enable clinical translation and use of this formulation for next generation nanomedicine for drug delivery, cancer-targeting, imaging and theranostic applications.
authors: Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: myallapu@uthsc.edu.
authors: Murali M
authors: MM
authors: Yallapu
authors: Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors: Neeraj
authors: N
authors: Chauhan
authors: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
authors: Shadi F
authors: SF
authors: Othman
authors: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
authors: Vahid
authors: V
authors: Khalilzad-Sharghi
authors: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors: Mara C
authors: MC
authors: Ebeling
authors: Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors: Sheema
authors: S
authors: Khan
authors: Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors: Meena
authors: M
authors: Jaggi
authors: Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: schauha1@uthsc.edu.
authors: Subhash C
authors: SC
authors: Chauhan
mesh_terms: D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055598:Chemical Phenomena; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D008819:Mice, Nude; D010316:Particle Size; D011485:Protein Binding / Q000187:drug effects; D055672:Static Electricity
chemical_list: D001672:Biocompatible Materials; D001798:Blood Proteins; D058185:Magnetite Nanoparticles
keywords: Cancer therapeutics; Drug delivery; Hyperthermia; Magnetic nanoparticles; Magnetic resonance imaging; Protein corona