Pancreatic cancer remains a formidable challenge due to limited treatment options and its aggressive nature. In recent years, the naturally occurring anticancer compound
juglone has emerged as a potential therapeutic candidate, showing promising results in inhibiting
tumor growth and inducing
cancer cell apoptosis. However, concerns over its toxicity have hampered
juglone's clinical application. To address this issue, we have explored the use of polymeric
micelles as a delivery system for
juglone in
pancreatic cancer treatment. These
micelles, formulated using
Poloxamer 407 and D-α-
Tocopherol polyethylene glycol 1000 succinate, offer an innovative
solution to enhance
juglone's therapeutic potential while minimizing toxicity. In-vitro studies have demonstrated that
micelle-formulated
juglone (JM) effectively decreases proliferation and migration and increases apoptosis in
pancreatic cancer cell lines. Importantly, in-vivo, JM exhibited no toxicity, allowing for increased dosing frequency compared to free drug administration. In mice, JM significantly reduced
tumor growth in subcutaneous xenograft and orthotopic
pancreatic cancer models. Beyond its direct antitumor effects, JM treatment also influenced the tumor microenvironment. In immunocompetent mice, JM increased immune cell infiltration and decreased stromal deposition and activation markers, suggesting an immunomodulatory role. To understand JM's mechanism of action, we conducted
RNA sequencing and subsequent differential expression analysis on
tumors that were treated with JM. The administration of JM treatment reduced the expression levels of the oncogenic
protein MYC, thereby emphasizing its potential as a focused, therapeutic intervention. In conclusion, the polymeric
micelles-mediated delivery of
juglone holds excellent promise in
pancreatic cancer therapy. This approach offers improved drug delivery, reduced toxicity, and enhanced therapeutic efficacy.