Figure 4

In vivo antitumor efficacy of SQgemcitabine NP. (A) Mice bearing pancreatic chemoresistent Panc1 orthotopic tumour model were treated with equivalent drug dose of gemcitabine (dFdC) or SQgemcitabine (SQdFdC). After 1 month of treatment, volume of the primary tumour and tumour extension were significantly reduced by SQgemcitabine showing its superior antitumour efficacy compared to physiological solution or vehicle nanoparticles treated (pure SQ) or gemcitabine treated mice. (B) Mice survival curves showed a significant enhancement of the median survival after SQgemcitabine treatment. All the gemcitabine treated and untreated mice died respectively within 64 and 47 days following tumour implantation. Remarkably, mice treated with SQgemcitabine were still alive after 3 months and no tumours were detected after autopsy. (C) Tumour biopsy samples were collected from each group of mice and used for immunohistochemistry examination. Paraffin sections submitted to hematoxylin-eosin (H.E) from SQgemcitabine treated mice revealed an absence of mitotic figures and demonstrated enlarged cells with significant necrotic changes. Tissues staining with terminal deoxynucleotidyltransferase (TUNEL), for detecting DNA fragmentation, and aspartic acid-specific cysteine proteases (CASPASE3), that are both present during apoptotic signaling cascades, revealed that apoptosis was most prominent in animals treated with SQgemcitabine. The number of Ki-67-positive tumour cells, a marker for proliferation, showed a significant decrease of the tumour proliferative activity in SQgemcitabine in comparison to gemcitabine treatment. (D) Quantitation rates of apoptotic cells confirmed the considerably increased apoptosis in the tumours from SQgemcitabine-treated mice and the statistically significant difference between SQgemcitabine and gemcitabine treatment. Adapted from ref 176. Copyright 2011 Nanomedicine.