Nanogels consisting of polyacrylamide (PAAm), crosslinked with dextranmethacrylate (Dex-MA), were designed to be partially biodegradable by enzymatic cleavage of the methacryl-functionalized polysaccharide chains. Important properties of the described hydrogels such as a low initial degree of swelling and a high crosslinking efficiency—in order to ensure the morphological integrity during nanogel preparation, purification and storage—are highly favored. Primarily, those requirements strongly depend on the amount of crosslinking points, i.e.methacrylategroups in the network. This parameter was adjusted by either increasing the ratio of Dex-MA/AAm for a fixed degree of substitution (DS) of Dex-MA or increasing the DS of Dex-MA for a fixed ratio of Dex-MA/AAm. Secondly, the distribution of crosslinking points in the network is another crucial parameter which was optimized by lowering the molecular weight of the Dex-MA for analogous DS or by simultaneously increasing the Dex-MA/AAm ratio and decreasing the respective DS. This resulted in nanogels with a reduced initial degree of swelling and sol content, therefore indicating a more homogeneous distribution of the same amount of crosslinking points. Degradation of the hybrid gel nanoparticles was examined by turbidity and DLS measurements upon treatment with dextranase. It was found that the degradation behavior depends on the total amount of methacrylategroups in the network and the degree of substitution of the individual Dex-MA chains.