Synthesis of MeOx/PheOzi-based copolymers with varying architecture (Fig. ) was performed by cationic ring-opening polymerization (CROP) of MeOx and PheOzi. While triblock and diblock architectures (pMeOx-b-pPheOzi-b-pMeOx, P_T, and pPheOzi-b-pMeOx, P_D) were realized by sequential monomer addition, a gradient microstructure (pMeOx-grad-pPheOzi, P_G) was obtained in a one-step procedure by concurrent copolymerization of MeOx and PheOzi (Sup. Fig. ). In addition, a star-like pPheOzi/pMeOx block copolymer ((pPheOzi-b-pMeOx)4, P_S) was prepared using the 4-arm initiator pentaerythritol tetrakistriflate. P_T, P_D and P_G were all designed to have a comparable amphiphilic ratio of 15 hydrophobic PheOzi to 70 hydrophilic MeOx units. For P_S, in turn, a degree of polymerization of 7.5 for PheOzi and 35 for MeOx per arm was targeted to ensure comparability. Analysis by size exclusion chromatography (SEC) revealed a narrow and essentially monomodal molar mass distribution for all four polymers, indicating successful syntheses (Sup. Fig. ). For further details regarding syntheses and characterization, the reader is referred to the supporting information (Sup. Fig. ). To enable a direct comparison of PEG and pMeOx as hydrophilic corona in the inverse thermogelling pPheOzi-based triblock copolymer system (Fig. ), a coupling procedure based on CuAAC was established. Our coupling strategy involved a difunctional alkyne-pPheOzi-alkyne derivative, which was prepared using propargyl tosylate as initiator and potassium pentynoate salt as terminating reagent in the respective CROP (Fig. , Sup. Fig. ). The successful synthesis of the desired homopolymer structure was evidenced by matrix-assisted laser-desorption-ionization time-of-flight mass spectrometry (MALDI-ToF MS) showing a very narrow molecular weight distribution (Fig. ) and the presence of essentially a single distribution of peaks with good agreement of obtained and calculated m/z values (Fig. ). The latter aspect implies that the use of propargyl tosylate and potassium pentynoate in CROP enables high initiation and termination efficiency. Thus, this strategy introduced here could be generally promising to obtain di-alkyne-functionalized POx and POzi derivatives. With the alkyne units on the pPheOzi homopolymer, an azide end group functionality was required for the hydrophilic polymers pMeOx and PEG. For pMeOx, the azide functionality was realized by terminating the respective CROP with NaN3 (Sup. Fig. ). PEG-N3, in turn, was obtained by quantitatively converting the hydroxyl group of commercially available mPEG-OH into an azide functionality following a literature procedure (Sup. Fig. ). In the CuAAC-based polymer coupling procedure (Fig. ), we used the azide-containing homopolymer in an excess (1.25 eq. per alkyne moiety) to ensure complete conversion of the pPheOzi alkyne moieties, thus reducing possible diblock copolymer by-product. To remove the remaining excess hydrophilic polymer from the coupling products, we -inspired from protein separationemployed salt-induced precipitation in combination with dialysis as purification method. Here, we utilized the fact that the pPheOzi-based triblock copolymers require lower (NH4)2SO4 salt concentration to precipitate in aqueous solution compared to the corresponding hydrophilic homopolymers. Success of this strategy was evidenced by SEC measurements, indicating effective removal of residual hydrophilic homopolymer (Fig. ). Finally, to separate any remaining salts, in particular residual copper salts, from the polymer product, we filtered solutions of the coupled triblock copolymers through a plug of SiO2/MgSO4 (Fig. ). This method has previously proven to be suitable for removing NaN3 from polymers and here also appears appropriate for removing copper salts. Thus, we obtained well-defined and comparable pMeOx-b-pPheOzi-b-pMeOx (P_pMeOx) and PEG-b-pPheOzi-b-PEG (P_PEG) triblock copolymers with minimal residual copper contents (27 ppm for P_pMeOx, 15 ppm for P_PEG). Of note, our coupling procedure is not limited to the examples presented here but can be applied to other azide-functionalized hydrophilic polymers. This is currently being utilized in our lab for the preparation of a larger block copolymer library. Detailed description of the polymer coupling and characterization can be found in the supporting information (Sup. Fig. ).