Design Rules for the Nano-Bio Interface of Nanodiamonds: Implications for siRNA Vectorization

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Kindermann, Marek | Neburkova, Jitka | Neuhoferova, Eva | Majer, Jan | Guricova, Miroslava | Benson, Veronika | Cigler, Petr

Edité par CCSD -

The enormous therapeutic potential of selective RNA interference has recently been manifested by the approval of several small interfering RNA (siRNA)-based drugs. However, the efficacy of siRNA delivery is still limited, and an extensive search for alternative and highly effective delivery approaches is ongoing. With this aim, three generations of non-viral vectors based on modified nanodiamonds (NDs) have been gradually developed in the past decade. They show great promise due to the negligible toxicity of the ND core. Here, a robust methodological approach is presented to enable the evaluation of new vector nanomaterials. Using a new type of third-generation ND vector coated with a copolymer with tunable charge density, variables such as colloidal stability, surface electrostatic properties, the molecular composition of the copolymer and the mode of complexation with siRNA are optimized. Using an innovative data processing strategy, the results are related to biological potency, toxicity and cell proliferation. Finally, the optimized composition of a coating copolymer consisting of a cationic component, 2-dimethylaminoethyl methacrylate, and an electroneutral biocompatible component, N-(2-hydroxypropyl) methacrylamide, is evaluated. The optimized NDs vectors are colloidally and biologically stable siRNA delivery tools with broad potential for RNA interference-based therapeutics.

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