Charge-reversible and pH-responsive biodegradable micelles and vesicles from linear-dendritic supramolecular amphiphiles for anticancer drug delivery

Recently, nanoparticles self-assembled from amphiphilic supramolecular linear-dendritic block copolymers (LDBCs) have attracted great interest, since the combination of linear and dendritic polymers can incorporate the unique properties of the different segments but avoid some inherent drawbacks of dendrimers, not to mention that the components can be flexibly adjusted to enrich their functionality. In this study, LDBCs formed by host–guest recognition of polyacetal dendrimers with a β-cyclodextrin core and adamantane-terminated zwitterionic poly(sulfobetaine) could self-assemble into micelles and vesicles by varying the hydrophilic/hydrophobic ratio. Owing to the acid-labile characteristic of the dendritic segments, the micelles and vesicles were degradable and could release their payloads in a pH-responsive manner. The incorporation of zwitterionic linear segments gave the micelles and vesicles a charge-reversal ability and excellent resistivity to protein absorption, leading to higher affinity to cell membranes than conventional PEG-coated nanoparticles. In addition, the potential of these nanoparticles as anticancer drug carriers was preliminarily evaluated by using doxorubicin as a model drug and the results indicated that the DOX-loaded micelles and vesicles exhibited remarkable anticancer activity. This study cast a new light on the application of dendrimers and these micelles and vesicles constructed from LDBCs may be promising candidates as anticancer drug delivery platforms for cancer therapy.