Self-assembly of synthetic macromolecules, inspired by the organization of biomolecules in nature, is a powerful approach for fabricating novel nanostructures, whose potential applications in nanomedicine are of significant interest. 1,2 Using amphiphilic linear copolymers as building blocks, various supramolecular architectures have been constructed, whose compositions, sizes, and morphologies are all tunable. [3][4][5] In spite of that, those nanostructures, made from synthetic macromolecules, are still primitive compared with those from biomolecules, which exhibit high complexity developed by evolution for millions of years. Our interest to attain nanostructures with higher complexities, approaching those of biological systems, drives our design of more types and sizes of macromolecular and nanoscopic building blocks, extending beyond simple linear block copolymers.Our initial targets are hetero-grafted diblock molecular brushes, 6,7 in which two different types of polymeric side chains are grafted sequentially along a backbone. These structures are designed as nanoscopic molecular frameworks having defined three-dimensional shape and control over the entire compositional profile, to mimic some features of the globular shape and compositional heterogeneities of protein building blocks. Three strategies are often used to synthesize molecular brushes: "grafting from", 8-11 "grafting onto", 12,13 and "grafting through". 14-18 The first two strategies can afford molecular brushes with relatively long and well-defined backbones. In the synthesis of hetero-grafted diblock molecular brushes, [19][20][21][22] for which the block segments of differing compositions are distributed along the primary molecular brush backbone, the "grafting through" strategy has several conveniences and advantages in avoiding many side reactions and providing significant structural control 6 due to the use of presynthesized polymers that are then polymerized to afford the final brush structure. To polymerize the highly diluted chain end groups of the polymers that ultimately become the grafted side chains, ring-opening metathesis polymerization (ROMP) is often applied. 14,15 Herein, by exploiting the orthogonality and livingness of reversible addition-fragmentation chain transfer (RAFT) polymerization 23 and ROMP, 24-26 we have developed a facile and efficient "grafting through" strategy to synthesize hetero-grafted diblock molecular brushes with precisely controlled architecture. These structures were transformed into amphiphilic diblock molecular brushes, which were then investigated as nanoscopic building blocks for the assembly of supramolecular nanostructures in aqueous medium.The amphiphilic hetero-grafted diblock molecular brush was produced by a highly efficient, one-pot "grafting-through" process, involving the sequential ROMP of norbornenylterminated macromonomers, followed by a deprotection reaction (Scheme 1). R-Norbornenyl poly(tert-butyl acrylate) (NB-PtBA) (1) and R-norbornenyl polystyrene (NB-PS) (2) macromonomers were firs...