Exhausting tumor associated macrophages with sialic acid-polyethyleneimine-cholesterol modified liposomal doxorubicin for enhancing sarcoma chemotherapy

Abstract To overstep the dilemma of chemical drug degradation within powerful lysosomes of tumor associated macrophages (TAMs), a sialic acid-polyethylenimine-cholesterol (SA-PEI-CH) modified liposomal doxorubicin (DOX-SPCL) was designed with both TAMs targeting and smart lysosomal trafficking. The modified liposome DOX-SPCL performed particle size as 103.2 ± 3.1 nm and zeta potential as −4.5 ± 0.9 mV with encapsulation efficiency as 95.8 ± 0.5%. In in vitro cell experiments, compared with conventional liposomal doxorubicin (DOX-CL) and PEGylated liposomal doxorubicin (DOX-PL), DOX-SPCL showed a selective binding on TAMs and a mere lysosomal concentration. In pharmacokinetic study, DOX-SPCL effectively impeded/delayed the disposition of mononuclear phagocyte system (MPS) with a value of AUC 0-t as 796.03 ± 66.93 mg L −1  h. In S180 sarcomas bearing mice, DOX-SPCL showed the greatest tumor inhibition rate (92.7% ± 3.6%) compared with DOX-CL (46.4% ± 2.0%) or DOX-PL (58.8% ± 7.6%). The