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Small. 2009 Nov;5(21):2424-32. doi: 10.1002/smll.200900578.

Controlling cellular uptake by surface chemistry, size, and surface topology at the nanoscale.

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Biomaterials and Tissue Engineering, The Kroto Research Institute, Department of Engineering Materials, University of Sheffield, Broad Lane, Sheffield S3 7HQ, UK.


Cell cytosol and the different subcellular organelles house the most important biochemical processes that control cell functions. Effective delivery of bioactive agents within cells is expected to have an enormous impact on both gene therapy and the future development of new therapeutic and/or diagnostic strategies based on single-cell-bioactive-agent interactions. Herein a biomimetic nanovector is reported that is able to enter cells, escape from the complex endocytic pathway, and efficiently deliver actives within clinically relevant cells without perturbing their metabolic activity. This nanovector is based on the pH-controlled self-assembly of amphiphilic copolymers into nanometer-sized vesicles (or polymersomes). The cellular-uptake kinetics can be regulated by controlling the surface chemistry, the polymersome size, and the polymersome surface topology. The latter is controlled by the extent of polymer-polymer phase separation within the external envelope of the polymersome.

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