Polyethylene glycol (PEG)-phospholipids in long-circulating liposomes cause non-specific immune reactions; mainly attributable to negatively-charged phosphoryl s at the interface of PEG and phospholipid. We investigated a novel lipopolymer, by which a superhydrophilic polymer (SHP) is conjugated to a non-phospholipid N1-(2-aminoethyl)-N4-hexadecyl-2-tetradecylsuccinamide (HDAS). The modification of preformed liposomes HDAS-SHP, HDAS-PEG2000, and DSPE-PEG2000 were performed by post-insertion techniques. The efficiency of post-insertion and desorption rates, from the liposome surface, were determined. HDAS-SHP micelles showed highly positive zeta potential (+28.4 mV); zeta potentials of DSPE-PEG2000 and HDAS-PEG2000 micelles were −34.4 mV, and −3.7 mV, respectively. Critical micelle concentration predicted amphiphilicity of HDAS-SHP (CMC 2.58 µM) as close to that of DSPE-PEG2000 (CMC 2.44 µM). Both HDAS-SHP and HDAS-PEG2000 post-inserted with comparable efficiency (79%, and 73%, respectively), but noticeably lower than DSPE-PEG2000 (90%). The desorption rate of HDAS-SHP was close to that of DSPE-PEG2000 (0.53%/h, and 0.45%/h, respectively); the desorption rate for HDAS-PEG2000 was slightly more at 0.67%/h. Compared to plain liposomes, both HDAS-SHP- and DSPE-PEG2000-liposomes showed significant leakage of encapsulated Na-fluorescein isothiocyanate (FITC) upon incubation with serum. At the same time, both modified liposomes were found to suppress serum levels of the complement proteins, Bb and C4d. We infer that HDAS-SHP is a viable alternative to commonly-used PEG-phospholipid derivatives for stealth purposes.

Location and extent of necrosis are valuable information in the management of myocardial infarction (MI). Methods. We investigated 2-deoxy-2-18F-fluoro glucaric acid (FGA), a novel infarct-avid agent, for positron emission tomography (PET) of MI. We synthesized FGA from commercially available 18F-fluoro-2-deoxy-2-D-glucose (FDG). MI was induced in mice by permanently occluding the left anterior descending coronary artery. Biodistribution of FGA was assessed 1 h after FGA injection (11 MBq). PET/CT was conducted 1 h, 6 h, 1 d, 3 d, and 4 d after MI. Subcellular compartment of FGA accumulation in necrosis was studied by tracing the uptake of biotin-labeled glucaric acid with streptavidin-HRP in H2O2-treated H9c2 cardiomyoblasts. Streptavidin-reactive protein bands were identified by LC-MS/MS. Results. We obtained a quantitative yield of FGA from FDG within 7 min ( radiochemical   purity > 99 % ). Cardiac uptake of FGA was significantly higher in MI mice than that in control mice. Imaging after 1 h of FGA injection delineated MI for 3 days after MI induction, with negligible background signal from surrounding tissues. Myocardial injury was verified by tetrazolium staining and plasma troponin (47.63 pg/mL control versus 311.77 pg/mL MI). In necrotic H9c2 myoblasts, biotinylated glucaric acid accumulated in nuclear fraction. LC-MS/MS primarily identified fibronectin in necrotic cells as a putative high fidelity target of glucaric acid. Conclusion. FGA/PET detects infarct early after onset of MI and FGA accumulation in infarct persists for 3 days. Its retention in necrotic cells appears to be a result of interaction with fibronectin that is known to accumulate in injured cardiac tissue.