Next-generation paclitaxel-nanoparticle formulation for pancreatic cancer treatment.

Published on Aug 1, 2019in Nanomedicine: Nanotechnology, Biology and Medicine5.182
· DOI :10.1016/J.NANO.2019.102027
Andrew E. Massey5
Estimated H-index: 5
(UT: University of Tennessee),
Mohammed Sikander7
Estimated H-index: 7
(UT: University of Tennessee)
+ 10 AuthorsSubhash C. Chauhan49
Estimated H-index: 49
(UT: University of Tennessee)
Sources
Abstract
Abstract Pancreatic cancer (PanCa) is a major cause of cancer-related death due to limited therapeutic options. As pancreatic tumors are highly desmoplastic, they prevent appropriate uptake of therapeutic payloads. Thus, our objective is to develop a next-generation nanoparticle system for treating PanCa. We generated a multi-layered Pluronic F127 and polyvinyl alcohol stabilized and poly-L-lysine coated paclitaxel loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PPNPs). This formulation exhibited optimal size (~160 nm) and negative Zeta potential (−6.02 mV), efficient lipid raft mediated internalization, pronounced inhibition in growth and metastasis in vitro , and in chemo-naive and chemo-exposed orthotopic xenograft mouse models. Additionally, PPNPs altered nanomechanical properties of PanCa cells as suggested by the increased elastic modulus in nanoindentation analyses. Immunohistochemistry of orthotopic tumors demonstrated decreased expression of tumorigenic and metastasis associated proteins (ki67, vimentin and slug) in PPNPs treated mice. These results suggest that PPNPs represent a viable and robust platform for (PanCa).
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