The present invention relates to a nanoparticle compn. comprising PLGA derivs. and a lipid. The compn. is suitable for medical use. Particularly, the present invention relates to a delivery system for delivery of drugs, in particular nucleic acids, with enhanced efficacy and reduced adverse effects, such as reduced toxicity and immunogenicity, on healthy tissue. More precisely, the present invention relates to a delivery system comprising hybrid nanoparticles comprising PLGA and lipidoids for the delivery of siRNA.