Authors: M. Thanou, A. Miller
Affilation: Imperial College London, United Kingdom
Pages: 354 - 356
Keywords: nanoparticle, cancer, siRNA delivery
RNAi therapeutics represent a method to treat human diseases by addressing targets that are not possible to be addressed with conventional medicines. In our Centre we design nanosized systems for siRNA delivery that consist of various components organised in concentric layers (ABCD nanoparticles). The core (A) consists of siRNA surrounded by a layer of de-novo prepared and commercially available lipids (B layer). The AB particle is surrounded by a polymer, C-layer (stealth) which is inserted in the lipid either as an amphiphile or post- coupled using aminoxy coupling techniques. The nanoparticles may be decorated (D-layer) with ligands targeting receptors found in solid tumours or in the liver using similar coupling methods. We have found that the molar composition of the ABCD components can have an effect on the efficiency of the nanoparticles to transfer siRNA in vitro or in vivo. We prepared nanoparticles that were able to substantially knock down genes on leukaemia cells (Jurkat) and primary human T-lymphocytes. The “in vivo” nanoparticle design is based on pharmacokinetic data obtained from ABCD nanoparticles bearing Gd3+ lipids and MRI. Such studies showed that neutral siRNA nanoparticles (~100nm) were able to accumulate intact (carrier and siRNA) in the tumour at 14h post administration.