Moreover, MMP-2/αVβ3 integrin complexes and MMP-9 are present at the surface of angiogenic blood vessels and cancer cells, respectively and their targeting by inhibitory peptides showed antitumor effects [147, 148]. MMP-targeting of Caelyx doxorubicin-loaded liposomes by insertion of a DSPE-PEG3400-CTT2 conjugate, the CTT2 peptide binding to MMP 2 and 9, led to increased doxorubicin accumulation in tumors and extended the survival of ovarian carcinoma xenograft-bearing mice over unmodified Caelyx Inhibitors,research,lifescience,medical liposomes [40]. 2.2.4. Small Molecule-Mediated Tumor Targeting Aberrant tumor growth is correlated

with a greater demand for nutrients relative to healthy organs and has been exploited for tumor targeting. To sustain their rapid growth, tumor cells overexpress Inhibitors,research,lifescience,medical folate receptor to capture the folate required for DNA synthesis [149]. The overexpression of folate receptor in cancers of several histology relative to normal tissues, the low cost of folic acid (FA), and the vast library of conjugation reactions available

make it one of the most used ligands for tumor-targeted drug delivery and tumor imaging (reviewed in [150]). Inclusion of a FA-PEG-DSPE Inhibitors,research,lifescience,medical conjugate into irinotecan-loaded liposomes enhanced drug concentration in tumors after intravenous injection over untargeted liposomes or free irinotecan resulting in the highest anticancer activity without detected side toxicity [41]. Similarly, folate-targeting of doxorubicin-loaded liposomes increased the survival of tumor bearing mice by 50% over untargeted liposomes [111]. Lee et al. used Inhibitors,research,lifescience,medical tetraiodothyroacetic acid, a competitive inhibitor of thyroid hormone binding to the endothelial cell integrin αVβ3, as a new ligand for tumor-targeted drug delivery. This ligand increased liposomal accumulation in tumors after intravenous injection and enhanced anticancer activity of the encapsulated anticancer drug

edelfosine [151]. Estrogen receptors are often this website overexpressed Inhibitors,research,lifescience,medical in breast and ovarian cancers and conjugation of the ovarian estrogenic hormone estrone to doxorubicin-loaded liposomes resulted in a dramatic increase in doxorubicin accumulation in breast tumors after intravenous injection over free drug or untargeted PEGylated doxorubicin-loaded liposomes (24.3 and 6.0-fold, resp.) resulting in the highest therapeutic activity [42, 112]. Similarly, conjugation Isotretinoin of a luteinizing hormone-releasing hormone (LHRH) analog to the surface of docetaxel-loaded liposomes increased docetaxel accumulation in ovarian xenografts by 2.86-fold over untargeted docetaxel-loaded liposomes with decreased liver and spleen capture though binding to the LHRH receptors highly overexpressed in ovarian cancer [152]. The basic fibroblast growth factor (bFGF) receptor is also overexpressed in several cancers [153].