School of Medicine Publications and Presentations
Document Type
Article
Publication Date
8-2019
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).
Recommended Citation
Massey, A. E., Sikander, M., Chauhan, N., Kumari, S., Setua, S., Shetty, A. B., Mandil, H., Kashyap, V. K., Khan, S., Jaggi, M., Yallapu, M. M., Hafeez, B. B., & Chauhan, S. C. (2019). Next-generation paclitaxel-nanoparticle formulation for pancreatic cancer treatment. Nanomedicine : nanotechnology, biology, and medicine, 20, 102027. https://doi.org/10.1016/j.nano.2019.102027
Publication Title
Nanomedicine
DOI
10.1016/j.nano.2019.102027
Academic Level
faculty
Mentor/PI Department
Immunology and Microbiology
Comments
Published by Elsevier Inc.