6533b838fe1ef96bd12a3b95

RESEARCH PRODUCT

Overcoming the barrier of CD8+ T cells: Two types of nano-sized carriers for siRNA transport

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Abstract Bioengineering immune cells via gene therapy offers treatment opportunities for currently fatal viral infections. Also cell therapeutics offer most recently a breakthrough technology to combat cancer. These primary human cells, however, are sensitive to toxic influences, which make the utilization of optimized physical transfection techniques necessary. The otherwise commonly applied delivery agents such as LipofectamineⓇ or strongly cationic polymer structures are not only unsuitable for in vivo experiments, but are also highly toxic to immune cells. This study aimed to improve the design of polymeric carrier systems for small interfering RNA, which would allow efficient internalization into CD8+ T-cells without affecting their viability and thereby removing the current limitations in the field. Here, two new carrier systems for small interfering RNA were tested. One is a cationic diblock copolymer, in which less than 10% of the monomers were modified with triphenylphosphonium cations. This moiety is lipophilic, promotes uptake and it is mostly known for its mitotropic properties. Furthermore, cationic nanohydrogel particles were synthesized in exceedingly small sizes (Rh Statement of significance This study provides insights into the design of polymeric delivery agents as the method of choice for overcoming the limitations of cell manipulation. Until now, CD8+ T-cells, which have become a treatment tool for currently fatal diseases, have not yet been made accessible for gene silencing by polymeric siRNA carrier systems. Choosing appropriate modification approaches for two chemically different polymer structures, we were, in both cases, able to achieve significant uptake in these cells even at low concentrations and without inducing cytotoxicity. These results remove current limitations and pave the way for bioengineering via gene therapy.