A general method to greatly enhance ultrasound-responsiveness for common polymeric assemblies

Ultrasound-controlled drug release is a very promising technique for controlled drug delivery due to the unique advantages of ultrasound as the stimulus. For this technique, the polymer assemblies that are sufficiently stable in the suspensions but dissociable under a gentle ultrasound treatment are very desirable. In most cases, such polymer assemblies were constructed by few specific polymers. Few examples of the polymer assemblies that are formed by common linear polymers while able to respond strongly to a gentle ultrasound treatment have been reported, because the chain entanglements within the assemblies resist efficiently the ultrasound-induced shearing force; notably, the ultrasound treatment should be gentle enough and incapable of breaking the polymer chains, otherwise it will damage biological tissues. In this study, we report that through intermediate intrachain-crosslinking of one block of a common diblock copolymer, and then self-assembly of the crosslinked polymer in the selective solvent for the uncrosslinked block, vesicles, worm-like micelles and spherical micelles that are highly regular and stable in the suspensions but dissociable under a gentle ultrasound treatment were prepared. The intermediate crosslinking restricts the chain entanglements within the assemblies remarkably, and thus enhances greatly ultrasound-responsiveness for the polymer assemblies. In addition, during the self-assembly, the as-crosslinked block chains are still flexible and less entangled and thus more dynamic, making the crosslinked polymer much more capable than its precursor in forming regular assemblies with various morphologies. Since most of common polymers either are crosslinkable or can be modified to be crosslinkable, this approach is a general method for preparing the strongly ultrasound-responsive polymer assemblies with different compositions, morphologies and structures.