Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer

Abstract

Prostate cancer is the most commonly diagnosed cancer disease in men in the Unites States and its management remains challenge in everyday oncology practice. Thus, advanced therapeutic strategies are required to treat prostate cancer patients. Curcumin (CUR) is a promising anticancer agent for various cancer types. The objective of this study was to evaluate therapeutic potential of novel poly(lactic-co-glycolic acid)- CUR nanoparticles (PLGA-CUR NPs) for prostate cancer treatment. Our results indicate that PLGA-CUR NPs efficiently internalize in prostate cancer cells and release biologically active CUR in cytosolic compartment of cells for effective therapeutic activity. Cell proliferation (MTS), clonogenic, and Western blot analyses reveal that PLGA-CUR NPs can effectively inhibit proliferation and colony formation ability of prostate cancer cells than free CUR. PLGA-CUR NPs showed superior tumor regression compared to CUR in xenograft mice. Further investigations reveal that PLGA-CUR NPs inhibit nuclear β-catenin and AR expression in cells and in tumor xenograft tissues. It also suppresses STAT3 and AKT phosphorylation and leads to apoptosis via inhibition of key anti-apoptotic proteins, MCL-1, Bcl-xL and caused induction of PARP cleavage. Additionally, PLGA-CUR NPs significant downregulation of oncogenic miR21 and up-regulation of miR-205 was observed with PLGA-CUR NPs treatment as determined by RT-PCR and in situ hybridization analyses. A superior anti-cancer potential was attained with PSMA antibody conjugated PLGA-CUR NPs in prostate cancer cells and a significant tumor targeting of 131I labelled PSMA antibody was achieved with PLGA-CUR NPs in prostate cancer xenograft mice model. In conclusion, PLGA-CUR NPs can significantly accumulate and exhibit superior anticancer activity in prostate cancer.

Polyphenols delivery by polymeric materials: challenges in cancer treatment

“…Furthermore, PLGA-PEG nanoparticles are able to enhance the anticancer efficiency of CUR in prostate (Yallapu et al, 2014) and colon (Kim et al, 2011) cancer cell both in vitro and in vivo. The enhancement of CUR activity was also reached by encapsulation into GL-based nanogels able to target the deliver the polyphenol to colon cancer due to pH responsivity (Madhusudana Rao et al, 2015).…”

Curcumin-encapsulated polymeric nanoparticles for metastatic osteosarcoma cells treatment

“…Many literatures have reported that PCL or PLGA could be served as compatible biomaterials to build nanocarrier-based delivery systems [38][39][40]. Herein, PCL was utilized to stabilize hydrophobic core, while mPEG-PLGA was used to improve the solubility of nanoparticles owing to pegylation [41][42][43][44][45] (Fig.…”

Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells

“…All glassware was cleaned with aqua regia (3 parts of concentrated HCl and 1 part of concentrated HNO3), rinsed with distilled water, ethanol and acetone, and oven-dried before use. Tetrachloroauric acid trihydrate (HAuCl4.3H2O), L-ascorbic acid (C6H8O6), sodium citrate (C6H5Na3O7.2H2O), sodium hydroxide (NaOH), 4,7,10,13,16,19,22,25,32 …”

“…Targeted delivery of therapeutics may help reduce toxicity and increase efficacy. Recently, novel nanomaterials tagged with relevant targeting ligands have been developed to interact with receptors highly expressed in tumour tissues for safe and efficient delivery of therapeutic cargos in the treatment of prostate cancer [4] [5] [6] [7].…”