DNA Carriers DOI: 10.1002/ange.200600214 Light-Regulated Release of DNA and Its Delivery to Nuclei by Means of Photolabile Gold Nanoparticles** Gang Han, Chang-Cheng You, Byoung-jin Kim, Rosemary S. Turingan, Neil S. Forbes, Craig T. Martin, and Vincent M. Rotello* Gene therapy is one of the most promising prospects in biomedical and bioorganic realms. [1] The success of gene therapy benefits mainly from having effective gene-delivery vectors for transporting plasmid DNA, small interfering RNA, or antisense oligonucleotides into target cells. The delivery of therapeutic nucleotides using nanomaterials such as polymeric micelles, [2] dendrimers, [3] nanorods, [4] nano- tubes, [5] and nanoparticles [6] is attracting increasing attention as a consequence of their unique dimensions and proper- ties. [7–10] Despitemuchprogress,unpackingDNAinsidetarget cells in a spatiotemporally controlled fashion is a major limiting factor in designing these artificial carriers. [11] Although several intracellular release strategies have been employed,includinglowpH, [12] highenzymeconcentration, [13] and redox materials inside the cells, [14] the use of light as an external stimulus represents a unique site- and time-specific means of unloading DNA. As such, photosensitive synthetic DNA carriers will provide new directions for gene delivery owing to the potential for versatile and facile chemical modifications and the modularity of the carrier–DNA com- plex. As a highly orthogonal external stimulus, photochemical processes enjoy wide use in surface patterning, [15] advanced materials, [16] biochemistry, [17] and drug-delivery systems. [18,19] Light-regulated methods uniquely limit the resultant biolog- ical effects to the illuminated areas with temporal control. [20] For example, biologically active molecules can be modified withphotosensitivegroupstobeessentiallybioinert;theycan then be reactivated by photointervention. [21] Such caged compoundshaveshowntremendousapplicationsinchemical [*] G. Han, Dr. C.-C. You, R. S. Turingan, Prof.Dr. C. T. Martin, Prof. Dr. V. M. Rotello Department of Chemistry, University of Massachusetts 710 North Pleasant Street, Amherst, MA 01003 (USA) Fax: (+ 1)413-545-4490 E-mail: Rotello@Chem.umass.edu B. J. Kim, Prof. Dr. N. S. Forbes Department of Chemical Engineering, University of Massachusetts Amherst, MA 01003 (USA) [**] This research was supported by the NIH (EB 004503(VR) and GM55002 (CTM)). Confocal images were taken at the Central Microscopy Facility at the University of Massachusetts at Amherst, whichissupportedbyagrantfromtheNationalScienceFoundation (NSF BBS 8714235). Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Angewandte Chemie 3237 Angew. Chem. 2006, 118, 3237–3241 # 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim