ABSTRACT
An ideal cancer therapy targets the tumor cells selectively without damaging healthy tissues. Even though the tumor-specific markers are limited, these molecules can be used for the delivery of anti-cancer drugs as an active targeting strategy. Since the lymphatic system plays a critical role in the dissemination of cancer cells, the drugs directed through lymphatics can feasibly reach to the sites of metastasis. LyP-1 is a peptide that binds to the p32 receptor which is highly expressed not only on the lymphatic endothelium but also on the malignant cells; thus, making this peptide ligand a preferable candidate to mediate active targeting of lymphatics and cancer cells. In this study, different formulations of LyP-1 containing lipid-based nanopharmaceutics so-called self-microemulsifying drug delivery systems (SMEDDS) were developed and tested for their efficacy in targeting breast cancer. Following the selection of non-toxic formulation, doxorubicin hydrochloride and LyP-1 were co-administered in the SMEDDS, which resulted in a significant increase in in vitro cytotoxicity in p32-expressing breast cancer cells, 4T1 and MDA-MB-231. Accordingly, the uptake of LyP-1 in the SMEDDS by the cancer cells was demonstrated. The expression of p32 was detected in the 4T1 tumor tissues which were efficiently targeted with LyP-1 in the SMEDDS. When doxorubicin was co-administrated with LyP-1 in SMEDDS via intraperitonial administration, tumor growth and metastasis were significantly reduced. In conclusion, a novel and efficacious SMEDDS formulation containing LyP-1 with a droplet size less than 100â¯nm was developed for the lymphatic targeting of breast cancer.
