Crystallization-driven layer-by-layer amphiphilic block copolymer co-assembly with planar cargo molecules

Self-assembly of block copolymers (BCPs) in selective solvents often provides promising routes for fabrication of morphologically rich microcarriers. Herein, a sort of lamellar platelet-like structure has been obtained through co-assembly of amphiphilic diblock polycarbonates and certain species of small molecules. The diblock copolymer consisted of a hydrophobic segment with pendent cholesterol groups and a hydrophilic block decorated with branched polyethylenimine groups, synthesized by sequential ring-opening polymerization. Planar drug molecules (such as curcumin, coumarin, and steroids) served as the nuclei that facilitated crystallization of hydrophobic block of copolymer chains with pendent cholesterol groups. Such small-molecule-mediated crystallization can force the copolymer chains to be fully stretched and packed in an orderly fashion, inducing the co-assembly of the diblock polycarbonate and cargo molecules, rather than the BCP self-assembly driven by solvent-philic/solvent-phobic interaction. The thickness of the co-assembled platelet was highly dependent on the chain length (degree of polymerization) of the copolymer, as well as the layer numbers of the stacking lamellae. Furthermore, such platelet-like co-assemblies effectively reduced the dosage-dependent cytotoxicity of curcumin. Overall, we herein propose a novel mechanism for small molecule induced macromolecular assembly and well-controlled morphological modulation through layer-by-layer stacking, which holds great potential for drug delivery in versatile biomedical applications.