Delivery of the anthracycline doxorubicin in tumor cells was indeed sub-optimal in its unmodified form due to its non-specific distribution PF-02341066 supplier in the untargeted regions, and hence severe side effects were observed [38]. Our in vivo studies have previously reported the tumor-specific bioaccumulation of the nanoparticles [26] and the current in vitro data presented here establish that PST-Dox nanoparticles readily delivers Dox into the human cancer cells as early as 2 h after

administration, probably owing to its small size compared with the clinically used analogue. In spite of the robust efficacy exhibited by the PST-Dox in vitro, we next evaluated antitumor effects in vivo in order to establish the therapeutic utility. DLA and EAC ascites tumor-bearing mice were evaluated on the 16th and 23rd day of the compound administration for the effects on body weight, tumor volume, viable

and non-viable tumor cell counts, and % ILS. Body weights were proportional to the age in weeks demonstrating no significant differences except in mice treated with Dox ( Table 1 for group 2; for others data not shown). Tumor reduction in DLA-bearing mice Akt inhibitor in terms of tumor volume was evident in all the groups except group 1 in comparison to the control group ( Figure 4A; Table 1; Supplementary Tables 1 and 2). Tumor reduction was highly significant in PST-Dox treated mice in group 2 (P < .0001), followed by group 4 (P < .001) and group 3 (P < .001) in comparison to the control. Dox treatment also reduced DLA tumor volume significantly in at least three groups (group 2, P < .0001; group 4, P < .001; group 3, P < .001 vs. control). Although PST001 as a single agent was effective, reduction in tumor volume was significant only in group 4 (P < .001) and group Molecular motor 2 (P < .001). As noted above, the compounds failed to reduce the tumor volume significantly in group 1, probably owing to a single day treatment regimen after tumor inoculation. Likewise, as observed in tumor reduction, % ILS was also highly significant in PST-Dox treated group 2, followed

by group 3 and group 4 (all three groups at P < .0001 vs. control) ( Figure 4B; Table 1; Supplementary Tables 1 and 2). Dox was also effective in increasing the life span in group 2, group 3 and group 4 (all three groups at P < .001), while PST001 was significant in group 4 and group 2 (P < .001). However, it is significant to note that PST-Dox also increased the life span in group 1 mice bearing DLA tumor (P < .01). The Kaplan-Meier survival curves of DLA mice treated with PST001, Dox or PST-Dox nanoparticles in different groups are shown in Figure 4C. PST-Dox treated mice group was highly significant (P < .001 vs. control), followed by Dox (P < .01) and PST001 (P < .01). Just as in the group 4, PST001 was slightly better than Dox with respect to the survival curves.