**5. Conclusions**

This paper, as well as previous studies, establish tyrosine-modified PPIs or PEIs as particularly promising polymeric systems for siRNA formulation and delivery. Low chemical complexity, as in the case of tyrosine modifications, and particularly defined structure and size, as in the case of PPI dendrimers, in combination with the optimal molecular weight (G4) may leave PPI-G4-Y as particularly promising for siRNA formulation.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2079-4991/10/9/1809/s1, Figure S1: Synthesis scheme and 1H-NMR analysis of PPI-G4-Y. Figure S2: Knockdown efficacies of various tyrosine-modified PPI- or PEI-based siRNA complexes. Figure S3: Knockdown efficacies upon storage of PPI-G4-Y/siRNA complexes at various temperatures for three days, in the presence of different FCS concentrations.

**Author Contributions:** Conceptualization, A.E. and A.A.; investigation, S.N., M.K., A.E.; resources, A.A.; writing—original draft preparation, S.N., M.K., A.A. and A.E.; writing—review and editing, A.E. and A.A.; supervision, A.E. and A.A.; funding acquisition, A.A. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by grants from the Deutsche Forschungsgemeinschaft (DFG; AI 24/21-1; AI 24/24-1) and the Deutsche Krebshilfe (70111616) to A.A.

**Acknowledgments:** The authors are grateful to Markus Böhlmann and Anne-Kathrin Krause for expert mouse maintenance, to Gabriele Oehme for help in cell culture experiments, the core unit "fluorescence technologies" (Kathrin Jäger) for cell sorting; Tamara Haustein (Institute for Organic Chemistry) for recording the NMR spectra.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
