Design And Assembly Of Dendron-like/linear Polypeptide-based Block Copolymers With Different Topologies

Owing to their biocompatibility, adjustable degradation profiles, thesecondary structure, hierarchical self-assembly and especially3-dimensionalarchitecture with high surface functional group density, both naturally branchedbiomacromolecules and artificial dendritic peptide mimetics attracted muchattention in biomaterials and nanomaterials. Meanwhile, due to their goodbiocompatibility, soft and network structures that mimic the extracellular matrix,and external stimuli-responsive properties, supramolecular and polymerichydrogels are being increasingly investigated for drug or gene delivery systems,tissue engineering, and various intelligent devices.First, dendron-like/linear/dendron-like poly(γ-benzyl-L-glutamate) triblockcopolymers with symmetrical topologies were synthesized via the combinationof ring-opening polymerization (ROP) of BLG-NCA and click chemistry. Theirmolecular structures and physical properties were characterized in detail bymeans of FT-IR, NMR, GPC, DSC, and WAXD. Notably, the triblockcopolymers could form thermo-reversible gels in toluene solution, and theirorganogelling mechanism was further studied by means of rheology, TEM, WAXD, SAXS, and AFM.Second, a new concept-the reverse micellar hydrogel-is introduced, and aversatile strategy is provided for fabricating supramolecular polypeptide-basednormal micellar hydrogel and reverse micellar hydrogel from the samepolypeptide-based copolymer via the cooperation of host-guest chemistry andhydrogen-bonding interactions. The supramolecular hydrogels were thoroughlycharacterized, and their self-assembly mechanism was proposed. Thesehydrogels can respond to dual stimuli, i.e., temperature and pH, and theirmechanical and controlled drug-release properties can be tuned by thecopolymer topology and the polypeptide composition. The reverse micellarhydrogel could load10%of the anticancer drug, doxorubicin hydrochloride(DOX), and sustain DOX release for45days, indicating that it could be usefulas an injectable drug delivery system.