- Maximize anticancer effects by combining organelle targeting with oxidation-reduction disturbance

- Research results are published in the world-renowned 'Chemical Engineering Journal (IF=13.2)' in the field of chemical engineering

△ Conceptual diagram of next-generation anticancer nano-platforms that combine organ targeting and oxidation-reduction disturbance

 A research team led by Professor Kang Han-chang of the Catholic University of Pharmacy (President Choi Jun-kyu) has developed a "next-generation anticancer nano-platform" that destroys the oxidation-reduction balance of cancer cells and precisely hits specific organelles, suggesting new possibilities for anticancer treatment.

 In general, drugs are accumulated in specific organelles according to their inherent properties to exert a drug effect. In particular, even drugs with the same chemical structure can be delivered to different organelles such as nuclei or mitochondria because hydrophilicity and hydrophobicity vary depending on the presence or absence of a salt. However, until now, there was a limit to the amount of inflow into the cell changed due to the difference in cell membrane permeability between drugs, and implementing precise organelles targetability.

 Professor Kang Han-chang's research team designed a diselenide (Se-Se) polymer-some (PSe₂-NP) nano-platform that selectively decomposes in the reduction environment of cancer cells to solve this problem. The platform is designed to implement different release rates in the cytoplasm by mounting hydrophilic drugs in the core and hydrophobic drugs in the membrane.

 The developed platform preemptively destroys the oxidation-reduction balance of mitochondria, an energy source for cancer cells, by consuming glutathione (GSH), an antioxidant, and increasing harmful active oxygen (ROS). Depending on the drugs installed in this process, two precise organelle targets are implemented. A platform equipped with a hydrophilic drug simultaneously induces redox disturbance and nuclear DNA damage in mitochondria, and a platform equipped with a hydrophobic drug focuses on mitochondrial electron transport system disturbance and functional damage.

 As a result of the research team's application to the colon cancer mouse model, the two nano-formulations recorded high tumor growth inhibition rates of 66% and 62%, respectively. In particular, the results of the combination index (CI) analysis between the drug and the carrier both confirmed a strong synergy effect (CI<1).

 The results of the study were published online on March 16 in the Chemical Engineering Journal (IF=13.2), a prestigious journal within the world's top 3% of chemical engineering, and were recognized for both academic and technical excellence. Meanwhile, the study was conducted with support from the Ministry of Science and ICT, the Korea Research Foundation, the Ministry of Health and Welfare, the Korea Institute of Health Industry Promotion, the Ministry of Education and the Institute of Basic Science Support.

 Professor Kang Han-chang of Catholic University, the head of the research, said, "Even drugs with the same chemical structure can change the polarity to control the target of organelles and simultaneously disturb the survival and death homeostasis of cancer cells with a nano platform to maximize drug effect synergy. We will continue research on next-generation nano platforms tailored to diseases in the future."

(Figure) Conceptual diagram of next-generation anticancer nano-platforms that combine organelle targeting and redox disturbance

By synthesizing poly(ε-caprolactone)-Se-poly(PSe₂-P), an amphiphilic polymer based on diselenide(Se-Se) binding that is selectively degraded in the reduction environment of cancer cells

It shows the structure and mechanism of action of the polymer somes (PSe₂-NP) formed in the aqueous phase.

In practical applications, HP@PSe₂-NP equipped with hydrophilic doxorubicin hydrochloride (HP) performs dual organelle targeting that causes nuclear DNA damage in addition to mitochondrial redox disturbance,

HB@PSe₂-NP equipped with a hydrophobic doxorubicin free base (HB) precisely strikes cancer cells through a single organelle-focused targeting that focuses on mitochondrial electron transport system disturbances and functional impairment.