In recent years, the development of biopharmaceuticals such as proteins and nucleic acids has intensified. However, low efficiency in delivering them into cells and a target tissue is a major challenge. Especially, drug delivery to kidney is one of the important challenges.

To overcome the above challenges, we recently developed drug delivery carriers for biopharmaceuticals using cyclodextrin (CD)-based aminated polyrotaxanes (transformable polymer). Polyrotaxane refers to a compound formed by threading an axile molecule through the cavity of numerous cyclic molecules and capping both ends with bulky functional groups. The cyclic molecules within the polyrotaxane are mobile along the axile molecule. Transformable polymer is a carrier in which the cyclic molecules (CD) in the polyrotaxane are modified with amino groups. Transformable polymer presents these amino groups on demand in response to the shape and charge distribution of proteins or nucleic acids, enabling strong interactions with biopharmaceuticals.

Consequently, transformable polymer enhanced intracellular uptake, facilitated escape from endosomes, and enabled intracellular release for various biopharmaceuticals, such as siRNA, antisense oligonucleotide, proteins, antibodies, antigens, mRNA, genome-editing molecules, etc. Importantly, transformable polymer showed superior delivery efficiency and safety compared to the commercially available carriers such as LipofectamineTM series, X-fect, and lipid nanoparticles (LNP). Furthermore, transformable polymer did not induce fever and anti-PEG antibodies after intravenous administration, although LNP did. Most importantly, transformable polymer delivered the biopharmaceuticals selectively to the kidney, with minimal distribution to the liver.

These results suggest that transformable polymer has the potential as a kidney targeting delivery carrier for biopharmaceuticals beyond LNP.