Circulation kinetics and biodistribution of dual-labeled polymersomes with modulated surface charge in tumor-bearing mice: Comparison with stealth liposomes

Polymersomes (Ps) based on poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PDLLA), with similar sizes (90–100 nm), but different zeta potentials (− 7.6 to − 38.7 mV) were prepared to investigate the effect of surface charge on blood circulation time and tissue distribution in tumor-bearing mice. For the in vivo studies dual labeled Ps were applied, which were obtained by encapsulating 3H-dextran 70 k in the aqueous core of Ps and by post-coupling of 14C-thioglycolic acid onto acrylated PEG chains of the Ps. Stealth liposomes (103 nm, − 6 mV) were used as a control. A substantial longer half lifetime (τ1/2) (47.3 h) and a reduced liver uptake (27.9% of injected dose (% ID)) of Ps with a zeta potential of − 7.6 mV were observed as compared to those of stealth liposomes (10.6 h, 39.8% ID) most probably due to the presence of a relatively thicker and denser PEG brush of the Ps as compared to the liposomes. As a result of their longer circulation times a high tumor accumulation of 18.6% ID was obtained for these Ps after 3 d circulation in mice while only 11.2% ID of stealth liposomes accumulated in the tumors as a result of their relatively short τ1/2 in blood. By increasing the zeta potential on Ps, more rapid clearance of Ps from the blood circulation was found due to an enhanced uptake by the liver. Importantly, co-localization of the two labels of Ps was observed during circulation indicating that dual labeled Ps were colloidally stable in blood without leakage of 3H-dextran. In conclusion, the results show that Ps with a slightly negative surface charge (zeta potential − 7.6 mV) are stable in the circulation and have longer circulation times and a higher tumor accumulation in mice than Ps with more negative zeta potentials or the stealth liposomes used as a control.

3H and 14C labeled polymersomes (a), Circulation kinetics of polymersomes (black, Ps) and stealth liposomes (white, SL) in mice (b) and tumor accumulation (% injected dose/gram) 3 d after injection (c).Figure optionsDownload as PowerPoint slide