Dual-Ligand Modification of PEGylated Liposomes Used for Targeted Doxorubicin Delivery to Enhance Anticancer Efficacy
Mannose receptor (CD206) and E-selectin are selectively expressed in M2-like tumor-associated macrophages (M2-TAMs) and activated endothelial cells of vessels surrounding tumor tissues. With the knowledge that d-mannose is the natural ligand of mannose receptors and l-fucose is the key calcium chelator for tumor-associated carbohydrate antigens (TACAs) binding to E-selectin, herein, we firstly reported d-mannose polyethylene glycol (PEG) conjugates (Man-PEG) and l-fucose PEG conjugates (Fuc-PEG) co-modified liposomal doxorubicin (DOX-MFPL) to improve tumor-targeting ability. The dual-ligand modified PEGylated liposomes (DOX-MFPL) were assessed by both in vitro and in vivo trials. Compared with the single-ligand d-mannose- or l-fucose-modified liposomes (DOX-MPL or DOX-FPL), DOX-MFPL achieved an increased distribution of DOX in tumor tissues. The antitumor study based on S180 tumor-bearing mice was conducted and the superior tumor inhibitory rate was shown with DOX-MFPL, probably owing to the superior tumor-targeting effect of DOX-MFPL and the modulation of the tumor microenvironment with the exhaustion of TAMs. In general, the dual-ligand drug delivery systems are expected to be promising in the development of specific and efficient methods for tumor treatment.
KEY WORDSdual-ligand mannose receptor E-selectin doxorubicin tumor targeting
This research was supported by the National Natural Science Foundation of China (No. 81573375), the National Natural Science Foundation of China (Grant No. 81703456), and the Liaoning Natural Science Foundation of China (Grant No. 201601140).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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