PST-Dox had the best effect compared to other compounds in reducing EAC tumor in the majority of the treatment regimen. Group 2 showed the highest effect (P < .0001) in terms of tumor volume reduction, followed by group 3 (P < .001) and group 4 (P < .001) compared to the respective control mice. Treatment with Dox was also effective in group 2 (P < .0001), followed by group 4 (P < .001) and group 3 (P < .001). PST001 alone was the least effective (P < .001 vs. respective control) among the three treatment groups which showed some tumor reduction. In EAC-bearing tumor mice, a maximum ILS of 240 ± 1.8% was observed on PST-Dox nanoparticle administration in group 2 ( Figure 5B; Table 1; Supplementary
Tables 1 and 2). Increment in the lifespan was highly significant in PST-Dox treated groups 2 and 3 (P < .0001 vs. control) followed by group check details 4 (P < .001 vs. control). ILS percent also corresponded with tumor reduction in nanoparticle treated mice. Although not comparable with PST-Dox, Dox also prolonged life span in groups 2, 3 and 4 (P < .001 vs. control). As seen earlier, PST001 was the least effective drug with ILS around 54% in group 4, followed by group 2 (both groups at P < .001 vs. control). Group 1 treatment regimen did not have significant improvement with respect to ILS in all the three drugs tested which is consistent with the tumor reduction seen in EAC cells. The Kaplan-Meier survival curves of EAC groups are shown in Figure 5C. PST-Dox treatment
was highly significant in groups 2, 3 and 4 compared to the corresponding control group (P < .001). Like in the previous data sets, Dox treatment Pexidartinib supplier (P < .01) was the next significant group, followed by PST001 in the Kaplan-Meier survival curves. In the ascites tumor models, it is clear that PST-Dox showed the best overall effect, especially when administered for several days before and after tumor inoculation. This points to the fact that PST-Dox is indeed efficient against tumors those are recently transplanted (days 2–15), next established (days 9–22) or have chances of recurrence (days 1–7). In the clinical scenario, this is relevant because the drug
could be effective in early, established and resected stages of the disease. Another aspect of this nanoconjugate is that they are a safer alternative compared to the parental Dox. In our studies, PST-Dox nanoparticles was found to be safer in animals with no indication of side-effects during the entire course of experiments in both the DLA and EAC ascites tumor models (Supplementary Figure 1). Even though Dox administration was effective and reduced the tumor burden, it was predominantly laden with visible signs of toxicity (Supplementary Figure 1). Majority of the animals treated with Dox showed severe weight loss, alopecia and cachexia, whereas PST-Dox treated mice appeared normal with no apparent signs of toxicity. We next evaluated the antitumor activity of PST-Dox nanoparticles in a syngenic EAC-induced solid-tumor mice syngraft.
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