Enhanced Toxicity of Gemcitabine by CD44 – Targeting Curcumin – Grafted Hyaluronic Acid Nanoparticles for Pancreatic Cancer

Enhanced Toxicity of Gemcitabine by CD44 – Targeting Curcumin – Grafted Hyaluronic Acid Nanoparticles for Pancreatic Cancer

Faculty of Pharmacy, Mahidol University

Title :

Enhanced Toxicity of Gemcitabine by CD44 – Targeting Curcumin – Grafted Hyaluronic Acid Nanoparticles for Pancreatic Cancer

Researchers :

Parichart Thummarati
Asst.Prof.Dr.Jiraphong Suksiriworapong
Dr.Krisada Sakchaisri
Prof.Dr.Varaporn Junyaprasert

Pancreatic cancer (PACA) is one of the deadliest cancers due to poor prognosis and treatment. To improve therapy, CD44, hyaluronic acid (HA)-binding receptors, overexpressing on PACA cells can be used as a target ligand for specific delivery of anticancer drugs. In this study, the synergistic effect of gemcitabine (GEM) and curcumin (CUR) has been investigated for enhanced efficacy of cancer treatment. For this purpose, we developed nanoparticles based on polymer-drug conjugates for dual delivery of GEM and CUR to improve specificity and efficacy of GEM for PACA treatment. CUR-grafted HA was linked with GEM via pH-sensitive linker and assembled to nanoparticles. The drug release of GEM and CUR was found to be specific and fast in acidic microenvironment while retarded at physiological pH. In vitro cytotoxicity study in PANC-1 cell lines revealed enhanced toxicity of the nanoparticles with IC50 of 2-fold lower than free drugs. Their toxicity was decreased after CD44 blockade treatment compared to untreated cells suggesting CD44 specific delivery of GEM. Therefore, the developed polymer-drug conjugates potentially improve efficiency of GEM which would be beneficial for PACA therapy.

Award Grant related to the Project : An award of Travel Grant for Ms. Parichart Thummarati at the 77th Annual Meeting of the Japanese Cancer Association, 27 – 29 September 2018, Osaka, Japan

Publishing : Presentation at the 77th Annual Meeting of the Japanese Cancer Association, 27 – 29 September 2018, Osaka, Japan

Key Contact Person :
Prof.Dr.Varaporn Junyaprasert
Faculty of Pharmacy, Mahidol University