Towards simultaneous drug and gene delivery using pH-responsive micelles from triblock terpolymers

• Applicant: Professorin Dr. Christine M. Papadakis, Ph.D.
• Subject Area: Experimental and Theoretical Physics of Polymers
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 574900016

Cancer remains one of the leading causes of death. For its cure, nucleic acid (gene) therapeutics has been successfully used. However, tailor-made carriers are required to protect the nucleic acids from the environment and to ensure their successful delivery to the tumor. Moreover, it is desirable to co-deliver (hydrophobic) chemotherapeutics or contrast agents for monitoring the distribution in the body. Such carriers are accessible via self-assembled micelles from biocompatible triblock terpolymers with a hydrophobic middle block having a low glass transition temperature, a positively charged end block and a hydrophilic poly(ethyleneglycol) (PEG)-like end block. The resulting micelles are expected to feature a soft hydrophobic core, which can accommodate the hydrophobic substances, and a positively charged shell, which can complex the negatively charged nucleic acids by electrostatic interaction, forming so-called “micelleplexes”. The PEG-like block reduces the toxicity and prevents aggregation of the micelles. We propose to use scattering methods to investigate the structures of such micelles as well as the structural changes during the uptake of the nucleic acid and the cancer drug. In detail, we use dynamic light scattering to determine the size of the micelles and to detect possible aggregation and (synchrotron) small-angle X-ray scattering to determine their shape, inner structure and aggregation behavior of the micelles. Moreover, we investigate the structural changes of such micelles upon loading with curcumin, a hydrophobic model drug, and upon simultaneous complexation of DNA. It shall be elucidated, how curcumin is distributed in the micelle and in which way DNA is complexed. Triblock terpolymers with different degree of ionization in the shell shall be used. At this, contrast variation in neutron small-angle neutron scattering shall be exploited. The length of the DNA will be varied, because too high lengths may lead to unwanted bridging of the micelles. The results will give insight into the role of the overall charge of the micelle, the degree of loading with drug, the mixing ratio with DNA and the length of the DNA. This will further the development of optimized carrier systems for gene therapy.

• DFG Programme: Research Grants
• International Connection: Greece
• Cooperation Partner: Dr. Stergios Pispas