2 research outputs found
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
Ī¼g/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<sup>+</sup> CD38<sup>ā</sup> CD123<sup>+</sup> 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<sup>+</sup> CD38<sup>ā</sup> CD123<sup>+</sup> LSC and non-LSC āleukemic blastā
compartments, without inducing myelosuppression or hemotoxicity. Besides,
NV also exerted excellent synergistic lethality against leukemic bone
marrow cells (BMC) at lower concentrations (0.1 Ī¼M) 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