Polymeric nanocapsules with cross-linked poly(2-hydroxyethyl methacrylate) and polystyrene blocks (PS-b-(c-PHEMA) nanocapsules) were synthesized via the surface initiated atom transfer radical polymerization and atom transfer nitroxide radical coupling reactions. With alkoxyamine bonds as the cross-linkers, the nanocapsules exhibited unique responsive behavior: When PBS and oxygen existed, these nanocapsules were broken down into pieces, which self-assembled into nanocapsules again when ascorbic acid was added. When PBS, ascorbic acid, and oxygen existed together, these nanocapsules self-assembled into larger capsules. However, both the nanocapsules and capsules would finally disintegrate into pieces as the time extended.