Well-Defined Nanoscopic Embedded Therapeutics Nystro€m and Wooley 23 Illum, L. Nasal drug delivery: new developments and strategies. Drug Discovery Today 2002, 7, 1184–1189. 24 Sun, C.; Lee, J. S.; Zhang, M. Magnetic nanoparticles in MR imaging and drug delivery. Adv. Drug Delivery Rev. 2008, 60, 1252–1265. 25 Sun, G.; Xu, J.; Hagooly, A.; Rossin, R.; Li, Z.; Moore, D. A.; Hawker, C. J.; Welch, M. J.; Wooley, K. L. Strategies for optimized radiolabeling of nanoparticles for in vivo PET imaging. Adv. Mater. 2007, 19, 3157–3162. 26 Xu, J.; Sun, G.; Rossin, R.; Hagooly, A.; Li, Z.; Fukukawa, K.; Messmore, B. W.; Moore, D. A.; Welch, M. J.; Hawker, C. J.; Wooley, K. L. Labeling of polymer nanostructures for medical imaging: Importance of charge density, spacer length, and crosslinking extents. Macromolecules 2007, 40, 2971–2973. 27 Welch, M. J.; Hawker, C. J.; Wooley, K. L. The advantages of nanoparticles for PET imaging. J. Nucl. Med. 2009, 50, 1743–1746. 28 Lee, N. S.; Sun, G.; Neumann, W. L.; Freskos, J. N.; Shieh, J. J.; Dorshow, R. B.; Wooley, K. L. Photonic shell-crosslinked nanoparticle probes for optical imaging and monitoring. Adv. Mater. 2009, 21, 1344–1348. 29 Sun, G.; Berezin, M. Y.; Fan, J.; Lee, H.; Ma, J.; Zhang, K.; Wooley, K. L.; Achilefu, S. Bright fluorescent nanoparticles for developing potential optical imaging contrast agents. Nanoscale 2010, 2, 548–558. 30 Du, W.; Nystrom, A. M.; Zhang, L.; Powell, K. T.; Li, Y.; Cheng, C.; Wickline, S. A.; Wooley, K. L. Amphiphilic hyperbranched fluoropolymers as nanoscopic 19F magnetic resonance imaging agent assemblies. Biomacromolecules 2008, 9, 2826–2833. 31 Du, W.; Xu, Z.; Nystrom, A. M.; Zhang, K.; Leonard, J. R.; Wooley, K. L. 19F- and fluorescently labeled micelles as nanoscopic assemblies for chemotherapeutic delivery. Bioconjug Chem 2008, 19, 2492–2498. 32 Nystrom, A. M.; Bartels, J. W.; Du, W.; Wooley, K. L. Perfluorocarbon-loaded Shell Crosslinked Knedel-like Nanoparticles: Lessons regarding polymer mobility and self assembly. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 1023– 1037. 33 Nystrom, A. M.; Xu, Z.; Xu, J.; Taylor, S.; Nittis, T.; Stewart, S. A.; Leonard, J.; Wooley, K. L. SCKs as nanoparticle carriers of doxorubicin: investigation of core composition on the loading, release and cytotoxicity profiles. Chem. Commun. (Cambridge, U.K.) 2008, 3579–3581. 34 Lin, L. Y.; Lee, N. S.; Zhu, J.; Nystrom, A. M.; Pochan, D. J.; Dorshow, R. B.; Wooley, K. L. Tuning core vs. shell dimensions to adjust the performance of nanoscopic containers for the loading and release of doxorubicin. J. Controlled Release 2011, in press. 35 Nystrom, A. M.; Wooley, K. L. Construction of thermoresponsive SCKs through tuning the crystalline melting point of the core domain. Soft Matter 2008, 4, 849–858. 36 Zhang, K.; Fang, H.; Shen, G.; Taylor, J.-S. A.; Wooley, K. L. Well-defined cationic shell crosslinked nanoparticles (SCKs) for efficient delivery of DNA or PNA. Proc. Am. Thorac. Soc. 2009, 6, 450–457. 37 Zhang, K.; Fang, H.; Wang, Z.; Li, Z.; Taylor, J.-S. A.; Wooley, K. L. Structure-activity relationships of cationic shell-crosslinked knedel-like nanoparticles: Shell composition and transfection efficiency/cytotoxicity. Biomaterials 2010, 31, 1805–1813. 38 Fang, H.; Zhang, K.; Shen, G.; Wooley, K. L.; Taylor, J.-S. A. Cationic shell-crosslinked knedel-like (cSCK) nanoparticles for highly efficient PNA delivery. Mol. Pharmaceutics 2009, 6, 615–626. 39 Zhang, K.; Fang, H.; Wang, Z.; Taylor, J.-S. A.; Wooley, K. L. Cationic shell-crosslinked knedel-like nanoparticles (cSCKs) for highly efficient gene and oligonucleotide transfection of mammalian cells. Biomaterials 2009, 30, 968–977. 40 Li, Y. L.; Du, W. J.; Sun, G. R.; Wooley, K. L. pH-responsive shell cross-linked nanoparticles with hydrolytically labile cross-links. Macromolecules 2008, 41, 6605–6607. 41 Zhang, Q.; Remsen, E. E.; Wooley, K. L. Shell cross-linked nanoparticles containing hydrolytically degradable, crystalline core domains. J. Am. Chem. Soc. 2000, 122, 3642–3651. 42 Iha, R. K.; Van Horn, B. A.; Wooley, K. L. Complex, Degradable Polyester Materials via Ketoxime Ether-Based Functionalization: Amphiphilic, Multifunctional Graft Copolymers and Their Resulting Solution-State Aggregates. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 3553–3563. 43 Van Horn, B. A.; Iha, R. K.; Wooley, K. L. Sequential and single-step, one-pot strategies for the transformation of hydrolytically degradable polyesters into multifunctional systems. Macromolecules 2008, 41, 1618–1626. 44 Li, Z.; Ma, J.; Lee, N. S.; Wooley, K. L. Dynamic cylindrical assembly of triblock copolymers by a hierarchical process of covalent and supramolecular interactions. J. Am. Chem. Soc. 2011, 133, 1228–1231. 45 Zhang, K.; Fang, H.; Li, Z.; Ma, J.; Hohlbauch, S. V.; Taylor, J.-S. A.; Wooley, K. L. Composite soft-matter nanoscale objects: Nanocylinder-templated assembly of nano- spheres. Soft Matter 2009, 5, 3585–3589. 978 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 969–978 ’ 2011 ’ Vol. 44, No. 10