Next-generation paclitaxel-nanoparticle formulation for pancreatic cancer treatment

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-naïve 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). In this study, we demonstrate the therapeutic efficacy of a novel PLGA-PTX nanoformulation (PPNPs). This system shows efficacy both in vitro and in vivo. Specifically, nanoindentation studies show an increased rigidity of PPNPs-treated pancreatic cancer cells, indicating reduced metastatic potential as confirmed with additional results herein (proliferation, colony formation, invasion, migration, cell cycle arrest, apoptosis induction). In vivo results indicate successful reduction in tumor growth, metastasis, and EMT markers in chemo-naïve and chemo-exposed orthotopic xenograft mice, suggesting that PPNPs may be a next-generation paclitaxel nanoformulation for PanCa treatment. [Display omitted]