Journal
CLINICAL HEMORHEOLOGY AND MICROCIRCULATION
Volume 74, Issue 3, Pages 267-279Publisher
IOS PRESS
DOI: 10.3233/CH-190641
Keywords
Polyamidoamine (PAMAM); dendrimer; nanoparticle; hemocompatibility; surface modification
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BACKGROUND: Polyamidoamine (PAMAM) dendrimers have been investigated for decades and currently applied in various areas throughout nanomedicine, including gene therapy, drug delivery, anti-bacteria and imaging. It is therefore necessary to assess cytotoxicity of PAMAM dendrimers systematically. Because blood component is usually the initial step of contact with any therapeutic agent, comprehensive hemocompatibility study is needed. MATERIALS AND METHODS: The triblock dendrimer: polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD), was successfully synthesized. Various in vitro assays to characterize hemocompatibility of both PAMAM (Generation 4.0) and PAMAM-PEG-cRGD were performed, including hemolytic assay, platelet activation examination, platelet counting, assessment of coagulating pathways and evaluation of complement system activation. RESULTS: The hemolytic ratio of PAMAM-PEG-cRGD maintained below 5%. Surface engineering of PEG and cRGD to PAMAM attenuated hemolysis and RBC aggregation as compared with unmodified PAMAM. PAMAM (Generation 4.0) reduced platelet counting in a dose-dependent manner, and the platelet number dropped dramatically at a relatively low incubating dose (1 mu M). Such surface modifications also alleviated platelet activation and platelet reduction mediated by PAMAM polycationicity. Finally, high concentration (10 mu M) of PAMAM interfered the coagulation system, prolonging prothrombin time significantly. CONCLUSION: Surface modification of PEG and cRGD to PAMAM (Generation 4.0) improves hemocompatibility. Introduction of PEG and cRGD significantly mitigates hemolytic and RBC aggregation effects as compared with unmodified PAMAM. Similarly, these modifications alleviate platelet activation and platelet reduction mediated by PAMAM polycationicity.
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