Scientists at the Osaka University in collaboration with Tokyo Tech have developed a new type of drug delivery system that uses a poly (ethylene glycol)–poly(lysine) block copolymer–ubenimex conjugate (PEG-b-PLys(Ube)). The utilization of this system has empowered an expansion in the centralization of ubenimex in target cancer stem cells.
CSCs are related to cancer progression and dissemination, so it’s necessary to eradicate CSCs in order to cure cancer. Scientists discovered that there were CD13 surface markers in hepatocellular carcinoma (HCC) stem cells.
Adding CD13 inhibitor ubenimex to cancer stem cells, HCC stem cells cause apoptosis (programmed cell death), becoming extinct. Be that as it may, in light of the fact that CSCs just live in part of tumor tissues, it’s imperative to build up a strategy for conveying drugs in high fixation to target sites.
The system combines the use of standard anticancer drugs, thus it can potentially decrease CSC.
Lead author Masamitsu Konno says, “First, we developed a DDS to deliver highly concentrated ubenimex and then, another DDS in which 20 ubenimex molecules were bound with poly (ethylene glycol)–poly(lysine) block copolymer conjugates.”
Scientists tried the method on mice by using intraperitoneal administration and intravenous injection of ubenimex. They found that the tumor size was significantly reduced. It suggested that it has become possible to deliver ubenimex to CSCs in high concentration.
Next, the combined administration of ubenimex and existing anticancer drugs (luorouracil (5-FU), cisplatin (CDDP), and doxorubicin (DXR)) was performed, enhancing apoptosis in vitro synergistically in CSCs in mice.
The corresponding author Hideshi Ishii says, “Our research results will promote the application of drugs whose medical effects on CSCs were verified but there were challenges in their delivery to target sites, which will promote repositioning, i.e., the drugs will be used to treat different diseases. Block copolymers used in the DDS in this study can be easily produced and exhibit strong effects, allowing them to be used for the application of other drugs as well.”
The research results were published in Oncogene.