Gemcitabine and Pin1 siRNA co-delivery with fucoidan-coated nano-liposomes for therapy of pancreatic cancer
Journal of Drug Delivery Science and Technology(2023)
摘要
Due to the malignant proliferation and severe tumor fibrosis of pancreatic cancer (PC), the efficacy of chemotherapy has been largely limited. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) promotes tumor progression by promoting collagen synthesis and tumor cell proliferation. In this study, we developed nano-liposomes (FU-GEM/Pin1 siRNA@LIP) that act simultaneously on pancreatic tumor cells. FU-GEM/Pin1 siRNA@LIP were designed with suitable particle size and potential, and effectively loaded with Pin1 siRNA and fucoidan (FU) while demonstrating good release stability and biocompatibility. Our study showed that FU-GEM/Pin1 siRNA@LIP effectively inhibited the proliferation of Panc01 and Panc02 tumor cells and significantly enhanced the uptake of these two types of cells in vitro. FU-GEM/Pin1 siRNA@LIP might cause tumor damage, promote apoptosis and reduce collagen formation in vivo. Molecular and histological studies demonstrated that FU-GEM/Pin1 siRNA@LIP regulated the expression of CDH11 and α-SMA, and also reducing collagen synthesis of peripheral matrix. In summary, our experiments highlight that FU-GEM/Pin1 siRNA@LIP is an effective combination delivery system. It can inhibit tumor cell proliferation in vitro, promote tumor cell apoptosis and reduce collagen synthesis in vivo. This system could provide a promising therapeutic option for PC.
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关键词
pancreatic cancer,gemcitabine,co-delivery,fucoidan-coated,nano-liposomes
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