## 3 Results and Discussion
### Boronate Ester Formation
The arrow indicates the shift occurring upon addition of increasing concentrations of PEG2000-PBA to ARS; **(b)** absorption of ARS and ARS-boronic esters in equilibrium at pH 7.4. The arrow indicates the shift occurring upon addition of increasing concentrations of Gal to ARS/PEG2000-PBA complex; **(c)** absorption of ARS and ARS/PEG2000-PBA boronic ester at pH 10.0. The arrows indicate the shift occurring upon addition of increasing concentrations of PEG2000-PBA to ARS; **(d)** absorption of ARS and ARS-boronic esters in equilibrium at pH 10. The arrows indicate the shift occurring upon addition of increasing concentrations of Gal to ARS/PEG2000-PBA complex. The constant for the formation of MeO-PEG\({}_{2000}\)-PBGal-PLA in principle can be obtained by displacement of ARS from the ARS/MeO-PEG\({}_{2000}\)-PBA complex. Because of the insolubility of the hydrophobic block in the aqueous analysis medium, it was not possible to determine it directly. Thus, the study was conducted using the water-soluble D-galactose, the moiety that would interact in the case of MeO-PEG\({}_{2000}\)-PBGal-PLA formation. Even if it is not accurately the same, the measures give a thermodynamic order of magnitude of the binding event. Exploration of the binding at neutral or basic pH can give hints about the best conditions to be applied for the two blocks coupling and the formation of MeO-PEG\({}_{2000}\)-PBGal-PLA nanoparticles. Therefore, the assay was conducted at two different pH: 7.4 and 10.0. The addition of increasing concentration of Gal to an ARS/MeO-PEG\({}_{2000}\)-PBA complex 1:1 solution reverted the trend observed before, giving a bathochromic shift of the band around 500 nm in the case of the experiment conducted at pH 7.4. At pH 10, the addition of Gal provoked an intensity increase in the band of the free ARS and a simultaneous decrease in the intensity of the band with a max at 413 nm of the ARS/MeO-PEG\({}_{2000}\)-PBA complex (Figure 4d). Results of the binding experiments of MeO-PEG\({}_{2000}\)-PBA with ARS and Gal are summarized in Table 2.  
The study reveals that the PBA moiety installed on PEG is able to interact with Gal and the overall affinities of the two different diols for MeO-PEG\({}_{2000}\)-PBA, ARS and Gal, are in agreement with what was previously reported [8; 14]. Moreover, the binding affinity was found to increase with increasing pH of the medium. In effect, the K value for Gal at pH 10 was considerably high (378 M\({}^{-1}\)), being around 90 times the K at pH 7.4 (378 M\({}^{-1}\)). It is evident that the best condition to form the desired assembly is an aqueous environment at pH 10. A first attempt was explored for the formation of nano-assemblies under these conditions by nanoprecipitation. \({}^{1}\)H NMR on the obtained samples revealed an extensive degradation of the polyester. Critical Issues of the Approach and Possible Solutions: Transforming the Idea into Working Nanoparticles  
Boronic acid responsive materials are fascinating and promising in many subfields of biomedical sciences such as biosensing and drug delivery. Accordingly with the method of preparation of those materials, different architectures and supramolecular constructs can be obtained, from crosslinked hydrogels to core-shell nanoparticles. Our approach, to the best of our knowledge, is the first example of a ligand presentation strategy combined and synchronized with the hydrophilic shell loss, which would solve the double dilemma discussed above. If from one side, the preliminary results discussed in this communication encourage us to further explore the approach, from the other side many critical issues emerged, and a contingency plan need to be developed to put at work this new idea. Three main problems have been identified: (1) limited efficiency of block functionalization; (2) oxidative susceptibility of B-C bond; (3) PBA/Gal ester formation between the two block and nanoparticles formation. Post-polymerization modification reactions have been used to distally modify the PEG chain with a PBA moiety.