Surface Charge Modification of Polyethyleneimine for Enhanced Renal Clearance and Bioimaging
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Polyethyleneimine (PEI) has emerged as a potentially effective carrier for gene delivery. To overcome the cytotoxicity of PEI in vivo, the biodistribution and clearance of PEI conjugated with near-infrared fluorophores (NIRF) were imaged in mice. To confirm the effect of surface charge on enhanced renal clearance, PEI was conjugated with three different types of NIRF: positively charged PEI-NIRF+, negatively charged PEI-NIRF-, and zwitterionic PEI-NIRF± conjugates, which were intravenously injected into mice. The biodistribution and body clearance were monitored under an NIR fluorescence imaging system at 4 h and 24 h postinjection. All organs and tissues were resected to further compare the distribution of each PEI-NIRF conjugate in two mice at 4 h and 24 h. The results showed that the zwitterionic PEI-NIRF± conjugate was most rapidly cleared, primarily through the kidneys of the mice within 24 h postinjection. In conclusion, the biodistribution of zwitterionic PEI-NIRF± was found to be significantly different from that of positively and negatively charged PEI-NIRF conjugates with increased renal clearance. Thus, zwitterionic PEI-NIRF± could be a promising gene delivery carrier that can potentially reduce the side effects of conventional cationic polymers such as cytotoxicity and non-specific binding in vivo.
Keywordspolyethyleneimine biodistribution renal clearance near-infrared fluorophores near-infrared fluorescence imaging
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