Drug Delivery System Targets Cancer Stem Cells

A research group in Japan has devised a drug delivery system that enhances the efficacy of inhibitors used to destroy cancer stem cells.

AsianScientist (Aug. 21, 2018) – Scientists in Japan have developed a drug delivery system that could be used to target cancer stem cells (CSCs) in liver cancer or hepatocellular carcinoma.

Cancer tissue cells are divided into two major groups: cancer cells and CSCs. The latter are believed to be responsible for cancer progression and dissemination, making it necessary to eradicate CSCs to prevent tumors from recurring.

In the present study, researchers from Osaka University and Tokyo Institute of Technology, Japan, sought a method to deliver ubenimex, an inhibitor of a molecule called CD13 on the surface of hepatocellular carcinoma stem cells. CD13 has been known to reduce levels of reactive oxygen species in hepatocellular carcinoma stem cells, promoting their survival in the body.

The researchers thus developed a drug delivery system to encapsulate ubenimex, creating a poly(ethylene glycol)-poly(lysine) block copolymer-ubenimex conjugate (PEG-b-PLys(Ube)). They showed that hepatocellular carcinoma stem cells exposed to PEG-b-PLys(Ube) accumulated high levels of reactive oxygen species resulting in increased programmed cell death (apoptosis) and reduced cell proliferation.

Next, the researchers performed intraperitoneal administration and intravenous injection of PEG-b-PLys(Ube) in tumor-bearing mice, demonstrating that tumor size was significantly reduced. They also showed that the administration of ubenimex in combination with existing anticancer drugs 5-fluorouracil, cisplatin and doxorubicin could synergistically enhance apoptosis of CSCs, in vitro and in mice models.

Corresponding author Professor Hideshi Ishii noted that the block copolymers used in this study can also be used to encapsulate and deliver other drugs that may otherwise be difficult to carry to specific target sites within the body, paving the way for more precisely-targeted therapy.



The article can be found at: Toshiyama et al. (2018) Poly(Ethylene Glycol)–poly(Lysine) Block Copolymer–ubenimex Conjugate Targets Aminopeptidase N and Exerts an Antitumor Effect in Hepatocellular Carcinoma Stem Cells.

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Source: Osaka University; Photo: Shutterstock.
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