Efficient Suppression of Liver Metastasis Cancers by Paclitaxel Loaded Nanoparticles in PDLLA-PEG-PDLLA Thermosensitive Hydrogel Composites.

Abstract

Breast and colonic carcinomas are two main origins of metastatic liver cancer. Chemotherapy, which introduces various anticancer drugs such as paclitaxel, is an important cure for patients who are not suitable for surgery and transcatheter hepatic arterial chemoembolization. However, the poor water solubility and serious side effects have limited the use of paclitaxel. Nanoparticles are promising carriers for paclitaxel to overcome these limitations. Besides, relatively consistent drug absorption by peritoneum into the liver through the portal system can be obtained if paclitaxel is given through intraperitoneum, which is beneficial to the therapy of metastatic liver cancer. In this study, we used our newly synthetic copolymer thermogels, PDLLA-PEG-PDLLA hydrogel as a carrier of paclitaxel-loaded nanoparticles. This novel injectable thermosensitive hydrogel is able to transfer into physically cross-linked non-flowing gel structure in body temperature with acceptable biocompatibility and biodegradability. The results showed that paclitaxel nanoparticle carried by PDLLA-PEG-PDLLA gel illustrated good liver metastatic cancer suppression efficacy. We also discussed the alterations of inflammatory cells (MDSCs and TAMs) and several inflammatory factors during the treatments. Nano-PTX-GEL led to more obvious reduction of infiltration of MDSCs in metastatic liver cancers, compared with free paclitaxel and Nano-PTX treated groups. In addition, we revealed that free paclitaxel treatment resulted in higher levels of IL-6, IL-10, PDL-1, TGF-β1, TNF-α and VEGF, while the expression levels of these inflammatory factors were much lower in the other two groups, especially in the Nano-PTX-GEL treated groups. These results suggested that utilization of PDLLA-PEG-PDLLA hydrogel as a carrier for paclitaxel could reduce inflammatory reaction induced by paclitaxel in liver metastatic cancers treatment. Besides, in this study, we used a simpler method to build liver metastatic cancer model through surgery, which can control the bias of results.