Biocorona Bound Gold Nanoparticles Augment Their Hematocompatibility Irrespective of Size or Surface Charge

Despite colloidal gold nanoparticles (AuNP) being proposed for a multitude of biomedical applications, there is a lack of understanding on how the protein corona (PC) formation over AuNP influences its interaction with blood components. Herein, 40 and 80 nm AuNP with branched polyethylenimine, lipoic acid, and polyethylene glycol surface coatings were exposed to human plasma, and time-dependent evolution of the PC was evaluated using differential centrifugation sedimentation. Further, the impact of PC-AuNP interaction with human blood components was studied by evaluating red blood cell (RBC) aggregation, hemolysis, platelet activation and aggregation, prothrombin time, activated partial thromboplastin time, complement activation and cytokine release. In contrast to bare AuNP, PC-coated AuNP exhibited enhanced compatibility with RBC, platelets, and lymphocytes. More importantly, PC-AuNP did not activate the platelet coagulation cascade or complement system or elicit an immune response up to a relatively higher dose of 100 μg/mL. This study suggests that, irrespective of the physicochemical properties, the adsorption of the PC over AuNP significantly influences its biological impact by alleviating adverse hematotoxicity of bare NP

Protein Nanomedicine Exerts Cytotoxicity toward CD34⁺ CD38^– CD123⁺ Leukemic Stem Cells

The efficacy of protein-vorinostat nanomedicine (NV) is demonstrated in leukemic stem cells (LSC) isolated from refractory acute myeloid leukemia (AML) patient samples, where it successfully ablated both CD34⁺ CD38^– CD123⁺ LSC and non-LSC “leukemic blast” compartments, without inducing myelosuppression or hemotoxicity. Besides, NV also exerted excellent synergistic lethality against leukemic bone marrow cells (BMC) at lower concentrations (0.1 μM) in combination with DNA methyltransferase (DNMT) inhibitor, decitabine. Considering the extermination of resilient LSC and synergism with decitabine, NV shows promise for clinical translation in the setting of a more tolerable and effective epigenetic targeted therapy for leukemia