Goren et al. utilized folate-targeted liposomes for treatment following injection of M109R-HiFR lung

tumor cells into mice [93]. Tumor cells were pretreated with liposomes ([DOX] = 10μM) and injected. The tumor weights after 35 days were 381mg for untreated mice, 397mg for mice treated with PEG liposomes (Doxil), and 57mg for mice treated with folate-targeted liposomes. The relative reduction in tumor size by the folate-targeted liposomes compared with untreated mice (~6.7-fold) was also greater than that observed here. However, a significant Inhibitors,research,lifescience,medical difference between our study and that of Goren et al. is the injection of the tumor cells after pretreatment with liposomes in the latter case. One would anticipate that the liposomes would have a greater effect on tumor growth if they interacted with the tumor cells prior to the initiation of the tumor in vivo. An apparent anomalous result from our study was the increased tumor size following nontargeted liposome treatment compared with saline control (Figure 8). Prior studies have Inhibitors,research,lifescience,medical typically

reported the opposite Inhibitors,research,lifescience,medical result. For example, Charrois and Allen compared DOX encapsulated Stealth (PEG) liposomes with saline control for treatment of 4T1 mouse mammary carcinoma [70]. Saline or 6mg/kg DOX encapsulated liposome was administered at day 4. At day 23, the tumor sizes were ~500mm3 for the saline treated mice and ~80mm3 for the liposome treated mice. In similar fashion, Han et al. compared DOX encapsulated PEG liposomes, DOX encapsulated comb-like polymer-incorporated liposomes, and PBS control for treatment of B16F10 inoculated

mice [94]. Mice were treated at day 6 with 6mg/kg DOX. At day Inhibitors,research,lifescience,medical 13, the tumor sizes were 300mm3 Inhibitors,research,lifescience,medical for PBS control and 50mm3 for the PEG liposomes and comb-like polymer liposomes. It is worth noting that, in our study, the differences between nontargeted liposomes and saline control were small at day 7 (Figure 8), which is similar to the result of Goren et al. reported above [93]. Also, the result at day 9 for the saline control is skewed lower due to one mouse treatment in which the tumor size decreased compared to day 7. The nanoDDS described in the present study possesses several features to enhance drug selectivity and availability. The targeting capabilities rely upon a ligand that is uniquely selective for the CSPG-modified form of CD44 [41]. Although modeled after a collagen-derived Fossariinae sequence, α1(IV)1263–1277PA is not click here recognized by the collagen-binding integrins found in melanoma (α1β1, α2β1, and α3β1). Thus, promiscuous receptor binding is avoided, unlike the use of HA for targeting CD44. The triple-helical nature of the ligand renders it reasonably stable to proteolysis, especially compared to other targeting molecules. The nanoDDS can also incorporate PEG to improve circulation time while minimally compromising cytotoxic activity.