Immunogenicity of bioactive magnetic nanoparticles: Natural and acquired antibodies

Abstract

Uniform magnetic nanoparticles (MNP) were prepared by nucleation followed by controlled growth of maghemite thin films onto porcine gelatin nuclei. The formed gelatin containing MNP (Gel-MNP) were then coated with dextran (Gel-MNP-Dex) followed by human serum albumin (Gel-MNP-Dex-HSA). Since these MNP are designated for clinical applications, studies concerning the immunogenicity of their antigenic components (porcine gelatin, dextran, and HSA) have been performed in BALB-C mice. These studies demonstrated that plasma of nonimmunized mice already contains basal levels of natural antibodies against all of these antigenic components. This work also demonstrated that the conjugated gelatin is a weak immunogen: Intraperitoneal injection of the various MNP (Gel-MNP, Gel-MNP-Dex dispersed in PBS emulsified with Incomplete Freund's Adjuvant (IFA) mineral oil and Gel-MNP-Dex-HSA dispersed in PBS) did not increase significantly the acquired anti-gelatin antibody titers. Exceptional behavior was observed following immunization with Gel-MNP-Dex-HSA dispersed in PBS emulsified with IFA, which exhibited an adjuvant effect and turned gelatin into a stronger immunogen. In contrast to gelatin, the conjugated HSA and dextran were found to be strong immunogens. The possibility that the various MNP will not induce an autoimmune response as a result of their clinical use is discussed in the contest of the protective role of the natural antibodies.

Novel magnetic fibrin hydrogel scaffolds containing thrombin and growth factors conjugated iron oxide nanoparticles for tissue engineering

“…10,40 Figure 1 describes the general scheme through which the physical conjugation of thrombin and the physical and covalent conjugation of bFGF onto the surface of the γ-Fe 2 O 3 nanoparticles were performed. Figure 1 illustrates that the covalent conjugation of bFGF to the γ-Fe 2 O 3 nanoparticles is based on the presence of gelatin thin layer on the surface of these nanoparticles, as shown in Figure 2A and B and described previously.…”

“…10,40 Briefly, 240 mg of gelatin were dissolved in 80 mL of water at 60°C. Then, 160 µL of a Fe +2 solution (10 mmol in 5 mL of 0.1 N HCl) and 57.6 µL of a sodium nitrite solution (7.27 mmol in 5 mL H 2 O) were added to the shaken gelatin solution.…”

Design of near-infrared fluorescent bioactive conjugated functional iron oxide nanoparticles for optical detection of colon cancer

“…NIR fluorescent iron oxide nanoparticles were prepared by a procedure similar to that described in our previous publication for the preparation of nonfluorescent iron oxide nanoparticles, 24 substituting the gelatin for CANIR covalently conjugated with gelatin. Briefly, 2 mg of CANIR was dissolved in 1 mL of water and added to 1 mg of EDC and 2.2 mg of sulfo-NHS dissolved in 1 mL of water.…”

“…[18][19][20][21][22] Previously, a unique type of uniform IO nanoparticles was prepared and characterized in our laboratory. 23,24 These IO nanoparticles were formed by controlled nucleation of IO onto gelatin, dissolved in an aqueous solution, and followed by stepwise growth of thin layers of IO films onto gelatin-IO nuclei. The same IO nanoparticles have been widely investigated in biological applications, and have been shown to be nontoxic.…”

Synthesis and Characterization of Thrombin Conjugated γ‐Fe2O3 Magnetic Nanoparticles for Hemostasis

“…[13][14][15][16] In our laboratory, we have developed maghemite (g-Fe 2 O 3 ) magnetic nanoparticles with a narrow size distribution ranging from a few nm up to approximately 100 nm (hydrodynamic size). [17][18][19] These nanoparticles are prepared by nucleation and then growth of thin magnetic g -Fe 2 O 3 layers on gelatin nuclei. Recently, it was shown that the conjugated gelatin is a weak immunogen: intraperitoneal injection of these g-Fe 2 O 3 nanoparticles dispersed in phosphate buffered saline (PBS) or emulsified with Incomplete Freund's Adjuvant (IFA) mineral oil did not increase significantly the acquired anti-gelatin antibody titers above the basal level of naïve mice.…”