New drug delivery materials have potential applications in cancer treatment
5-fluorouracil (5-FU) is an anticancer drug indicated for use in the treatment of some common cancers such as colon cancer, esophageal cancer, stomach cancer, pancreatic cancer, pancreatic cancer, head and neck cancer and breast cancer. The mechanism of action of this drug is based on irreversible inhibition of the enzyme thymidylate synthase, while causing incorrect synthesis in cancer cells. 5-FU is mainly used intravenously due to its poor absorption from the gastrointestinal tract. After injection of 5-FU, the drug is distributed and eliminated rapidly with a half-life of about 8-20 minutes. Therefore, researching smart materials to protect 5-FU used intravenously is an important research direction in creating smart and targeted drugs.
The research team conducted the project with the goal of finding a new drug carrier system based on AuNPs and a modified cyclodextrin (CD) derivative containing the NH2 functional group with special properties, such as effective durability and ability to control drug release from the carrier system.
Drug delivery mechanism of AuNPs/CD-SH.5
Through the research process, Associate Professor, Dr. Dang Chi Hien and his colleagues have successfully synthesized three cyclodextrin derivatives containing free amine groups modified from CD: Mono-6-amino-deoxy-6-β-cyclodextrin (CD-NH2), Mono-6-( 1,3-trimethylenediamine)-6-deoxy-β-cyclodextrin (TMACD) and Mono-6-(1,6-hexamethylenediamine)-6-deoxy-β-cyclodextrin (HMACD).
At the same time, scientists synthesized three nanocomposite systems based on AuNPs and β-cyclodextrin derivatives (CD, HPCD and TMACD) and determined the physicochemical properties of the materials.
The research team's testing and evaluation process showed that the drug 5-FU was successfully delivered onto nanocomposite systems based on AuNPs and β-cyclodextrin derivatives (CD, HPCD and TMACD). The team determined the physicochemical properties of the materials and compared them with a drug-free system. The results show that the AuNPs/TMACD system has the best drug delivery efficiency.
The drug delivery Nano system in the study has the ability to release drugs and has the ability to protect drugs well in the physiological blood environment (pH 7.4). The mechanism of drug release is through swelling of the cyclodextrin molecule, and the Fickian diffusion mechanism is a contributing factor in controlling drug release.
Associate Professor, Dr. Dang Chi Hien and the research team tested the biological activity of all derived materials. The results showed that all derived materials in the study (CD-x and AuNPs/CD-x) were not toxic to normal cells. The two nanocomposite systems 5-FU@AuNPs/CD and 5-FU@AuNPs/TMACD showed good inhibition on the MCF-7 breast cancer cell line, in which 5-FU@AuNPs/TMACD showed superior activity.
These findings highlight the significant potential of amine-derivative cyclodextrin-shelled AuNPs as exceptionally effective carriers for anticancer drugs, offering promising applications in both diagnostics and therapeutics.
Method for manufacturing drug-carrying nanocomposite materials (A) and drug binding performance and drug loading performance of different materials (B).
The research team's success will be an important premise to guide the application of creating new nanometer-sized materials with good dispersion in physiological environments, effective applications in the field of biomedicine and drug delivery, with high safety, non-toxic, and biocompatible. With that desire, scientists plan to continue testing in vivo the cytotoxicity of two nanocomposite materials: 5-FU@AuNPs/CD and 5-FU@AuNPs/TMACD. At the same time, the group will research and develop the synthesis of two nanocomposite materials on a pilot scale.
The project has been graded Excellent by the Acceptance Council of the Vietnam Academy of Science and Technology.
Translated by Quoc Khanh
Link to Vietnamese version
