Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 8, Pages 10015-10029Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c21997
Keywords
pancreatic cancer; intraperitoneal delivery; nanoemulsion; CXCR4; nerve growth factor
Funding
- University of Nebraska Medical Center (UNMC)
- NIH [R01 CA235863]
- NIH Nebraska Center for Nanomedicine Center for Biomedical Research Excellence (COBRE) [P30 GM127200]
- National Institute for General Medical Science (NIGMS) [INBRE.P20 GM103427, COBRE. P30 GM106397]
- National Cancer Institute (NCI) [P30 CA036727]
- Nebraska Research Initiative
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Pancreatic cancer progression relies on the nervous tumor microenvironment. This study utilized cationic perfluorocarbon nanoemulsions to deliver therapeutic siRNA and silence nerve growth factor (NGF) expression in orthotopic pancreatic tumors. The nanoemulsions achieved deep tumor penetration, enhanced NGF gene silencing, and effectively suppressed tumor growth in vivo and in vitro compared to control polycation/siRNA polyplexes. Delivery of NGF siRNA using nanoemulsion is a promising treatment approach for pancreatic cancer by targeting the tumor-neuronal interactions.
Pancreatic cancer (PC) is a fatal human cancer, whose progression is highly dependent on the nervous tumor microenvironment. In the present study, cationic perfluorocarbon nanoemulsions were employed as an intraperitoneal delivery platform to facilitate the delivery and penetration of a therapeutic small interfering RNA (siRNA) to orthotopic pancreatic tumors. The nanoemulsion was used to silence the expression of the nerve growth factor (NGF) as a way of favorably modulating the tumor-neuronal interactions in pancreatic tumors. The nanoemulsions exhibited deep tumor penetration that was dependent on exocytosis and enhanced NGF gene silencing in vitro and in vivo when compared with control polycation/siRNA polyplexes, leading to the effective and safe suppression of tumor growth in orthotopic PC. Overall, emulsion-assisted delivery of NGF siRNA is a promising treatment approach for PC by targeting the interactions between the tumor cells and the nervous microenvironment.
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