Drug delivery Nanoengineered Polymer Capsules: Tools for Detection, Controlled Delivery, and Site-Specific Manipulation** Gleb B. Sukhorukov,* Andrey L. Rogach, Bernd Zebli, Tim Liedl, Andre G. Skirtach, Karen Kçhler, Alexei A. Antipov, Nikolai Gaponik, Andrei S. Susha, Mathias Winterhalter, and Wolfgang J. Parak Keywords: · biomaterials · drug delivery · microcapsules · polyelectrolytes · quantum dots Introduction The interdisciplinary field of nanobiotechnology merges a number of disciplines. One aim is the discovery of new drugs and their delivery systems, as for example to build up multifunctional capsules as intelligent drug carriers: once in- jected somewhere into the bloodstream the capsules would find their target, repair or kill the damaged cells, report the diagnostics, and leave the site without any further damage. It seems that such promises could only be a subject for sci- ence fiction but in fact it is becoming a realistic project, which, of course, still requires a wide range of innovations. On the experimental side much progress has been achieved in the fabrication and engineering of nano- and microcarri- ers and their subsequent functionalization. The next step is to combine different functions into one carrier, thus provid- ing new types of delivery systems. This would allow for more efficient drug transport by guiding the carriers to des- ignated types of cells or tissues. Furthermore, such carriers could also monitor the pH conditions or the temperature and, upon external triggering, start a chemical reaction at a predefined site. Specifically designed and encapsulated ma- terials and surfaces would contribute to improved specificity and allow a reduction in total drug concentration with fewer side-effects. Such systems would provide a tool for the con- trolled delivery of drugs to cells or specific parts of tissue. In other areas, for instance in implantology and tissue engi- neering, carrier systems are of interest due to the possibility of the slow release of drugs to support healing and integra- tion. A large number of different artificial delivery systems are known today. Typical examples are based either on solid micro- and nanoparticles, as well as on liposomes able to entrap drug molecules or polymeric vesicles made by self- organization or interfacial polymerization. [1, 2] The next step is to release the container contents to a predefined site. Tar- geting capsules on the molecular level can be achieved by the specific linking of peptides or proteins and/or sugars to their outer surface, thus allowing selective binding to cell components. [3, 4] Recently, [5a] specific delivery of relatively large (5 mm) colloidal particles functionalized with arginine– glycine–aspartic acid (RGD) receptors into cells was dem- onstrated. After internalization by cells the particles are transported to lysosomes to be digested by proteolytic en- zymes. The stability or protection of introduced molecules becomes an important factor. Polymeric vesicles enable the protection of encapsulated substances for a certain period of time, that is, while they are captured in lysosomes. The [*] Dr. G. B. Sukhorukov, Dr. A. G. Skirtach, K. Kçhler, Dr. A. A. Antipov Max Planck Institute of Colloids and Interface 14424 Potsdam/Golm (Germany) Fax: (+ 49) 331-567-9202 E-mail: gleb@mpikg-golm.mpg.de Dr. A. L. Rogach, Dr. A. S. Susha Photonics & Optoelectronics Group Physics Department and Center for Nanoscience (CeNS) Ludwig-Maximilians-Universität München Amalienstr. 54, 80799 Munich (Germany) B. Zebli, T. Liedl, Dr. W. J. Parak Center for Nanoscience (CeNS) Ludwig-Maximilians-Universität München Amalienstr. 54, 80799 Munich (Germany) Dr. N. Gaponik Institute of Physical Chemistry University of Hamburg Grindelallee 117, 20146 Hamburg (Germany) Prof. Dr. M. Winterhalter International University Bremen School of Engineering and Science, 28759, Bremen (Germany) and Institut de Pharmacologie et de Biologie Structurale 205, rue de Narbonne, 31077 Toulouse (France) [**] This work is supported by the Volkswagen Foundation (I/80 051- 054). Prof. Dr. H. Mçhwald is greatly acknowledged for his con- tinuous support of this research. Parts of this project were also supported by the DFG (Emmy Noether program WJP). 194  2005 Wiley-VCH Verlag GmbH & Co. KGaA, D-69451 Weinheim DOI: 10.1002/smll.200400075 small 2005, 1, No. 2, 194 –200 concept