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Cellular and subcellular targeted delivery using a simple all-in-one polymeric nanoassembly.

Nanocarrier-mediated drug delivery is a promising strategy to maximize the power of chemotherapy and minimize undesirable side effects. However, current approaches show insufficient drug loading capacity, inefficient drug release, and complex post-modification processes. Platforms that attempt to enhance one of the features often compromise other merits. We describe here a simple and robust block copolymer assembly system that offer the combination of desirable characteristics. The design of self-immolative and crosslinkable hydrophobic moieties offer stable and high encapsulation. Redox triggerable polymer self-immolation promotes drug release by switching the hydrophobic core into completely hydrophilic chains. The reactive amine handles, presented on their surface, allow simple 'plug to direct' post-modification with a variety of ligands for targeting. Functionalized nanoassemblies have been programmed to home in specific sub-cellular compartments such as the cytosol, the mitochondria, and the nucleus. The simplicity, versatility and efficacy of the system open up possibilities for an all-in-one delivery system.