A New Approach to Release Insoluble Curcumin into DU-145 Human Prostate Cancer Cells Through Biodegradable Polymeric Nanocarriers with Apoptosis Induction and Metastasis Inhibition

Objective: Curcumin (C₂₁H₂₀O₆, CUR) is the most abundant compound in turmeric (Curcuma longa), which had antioxidant, anti-cancer and anti-inflammatory activities. Due to its low solubility in water, the aim of study was design and synthesis of PEG400-OA nanocarriers for increasing curcumin solubility and its delivery to cancer cells. Methods: In this study, curcumin was formulated into biodegradable poly (ethylene glycol)-oleate (PEG400-OA) nanocarriers. Physicochemical property of curcumin in nanoparticles (CLNs) was measured. Apoptotic and anti-invasive effects of curcumin in nanoparticles were evaluated in DU-145 cancer cells. Results and Discussion: The micelles/liposomes with a size of about 20.5–35.5 nm showed a CUR-loading efficiency of 91.7 and loading content of 4.0. In vitro release of CUR from the CLN composite was evaluated at pH values of 5.0 and 7.4 by dialysis method. It was observed that CLN possesses sustained release behavior for at least 3 days with a high extent of drug release in acidic media. Besides, the CUR release increased slightly at higher temperatures. CLNs significantly decreased DU-145 cell viability in a dose-dependent manner (IC₅₀ 42.54 µg/mL) and effectively inhibited cell migration. CLNs (42.54 µg/mL) significantly upregulated apoptotic genes CASP8 and CASP9, and EMT inhibitor gene E-cadherin in DU-145 cells. In addition, downregulation of EMT-involved genes including B-catenin, TGFB1, and SMAD3 was revealed after CLNs induction. Conclusions: Our results suggested that PEG400-OA nanocarriers as stable, biodegradable and soluble noncarriers in body fluids can used in therapeutic strategies to drug delivery. In addition, this noncarrier can increased anticancer effect of curcumin in prostate cancer cells.