Technical Feature

Technical Feature

Nanoparticle Delivery: Targeting and Nonspecific Binding

Rihe Liu, Brian K. Kay, Shaoyi Jiang and Shengfu Chen


Targeted cancer therapies focus on molecular and cellular changes that are specific to cancer and hold the promise of harming fewer normal cells, reducing side effects, and improving the quality of life. One major challenge in cancer nanotechnology is how to selectively deliver nanoparticles to diseased tissues while simultaneously minimizing the accumulation onto the nanoparticle of unwanted materials (e.g., proteins in the blood) during the delivery process. Once therapeutic nanoparticles have been created, very often they are linked or coated to other molecules that assist in targeting the delivery of nanoparticles to different cell types of the body. These linkers or coatings have been termed targeting ligands or “smart molecules” because of their inherent ability to direct selective binding to cell types or states and, therefore, confer “smartness” to nanoparticles. Likewise, “smartness” can be imparted to the nanoparticles to selectively repel unwanted entities in the body. To date, such smart molecules can consist of peptides, antibodies, engineered proteins, nucleic acid aptamers, or small organic molecules. This review describes how such smart molecules are discovered, enhanced, and anchored to nanoparticles, with an emphasis on how to minimize nonspecific interactions of nanoparticles to unintended targets.

Rihe Liu Rihe Liu can be reached at the Eshelman School of Pharmacy at the University of North Carolina, Chapel Hill, NC 27599, USA; tel. 919–843–3635; and e-mail

Liu is an associate professor of medicinal chemistry and genome sciences at the University of North Carolina, Chapel Hill. He received his BSc degree in polymer physics from the University of Science and Technology of China (1988) and his PhD degree in biochemistry from the University of California, San Diego (1996). From 1997 to 2001, Liu was a postdoctoral fellow at the Harvard Medical School/Massachusetts General Hospital and Howard Hughes Medical Institute. He joined the faculty of the University of North Carolina, Chapel Hill in December 2001. His research interests include the identification and investigation of proteins with desired biological functions from natural proteome libraries, identification of drug targets using chemical biology approaches, and screening for bio-marker-binding affinity molecules from synthetic peptide or protein domain libraries using in vitro protein selection strategies.

Brian Kay can be reached at the University of Illinois, Chicago, IL 60607–7060, USA; tel. 312–996–4249; e-mail:

Kay received his PhD and postdoctoral training at Yale University and the National Institutes of Health, respectively. He has been on the faculty at the University of North Carolina—Chapel Hill, University of Wisconsin-Madison, and Argonne National Laboratory before joining the Department of Biological Sciences as professor and head at the University of Illinois, Chicago, in 2005. His research interests include mapping protein-protein interactions with combinatorial peptide libraries, antibody engineering, designer affinity reagents, biosensors, and biotechnology.

Shaoyi Jiang can be reached at the Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA; tel. 206–616–6509; fax 206–685–3451; and e-mail

Jiang is the Boeing-Roundhill Professor of Chemical Engineering and Adjunct Professor of Bioengineering at the University of Washington, Seattle. He received his PhD degree in chemical engineering from Cornell University in 1993. He was a postdoctoral fellow at the University of California, Berkeley, between 1993 and 1994 and a research fellow at California Institute of Technology between 1994 and 1996 both in chemistry. His research focuses on biomolecular interfaces, biomaterials, and biosensors, particularly the molecular understanding, design, and development of zwitterionic-based materials for biomedical and engineering applications.

Shengfu Chen can be reached at the State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhenjiang University, Hangzhou, Zhejiang, 310027, P.R. China; tel. 86–571–87953013; fax 86–571–88981187; and e-mail

Chen is a professor at the State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhenjiang University (ZJU), Hangzhou, Zhejiang, P.R. China. He received his PhD degree from the Shanghai Institute of Applied Physics, Chinese Academy of Sciences in 1998 and was a research associate at the University of Washington, Seattle, before joining the faculty of ZJU in 2007. His current research focuses on investigating interfacial phenomena and properties of biological and chemical systems at the nanometer scale and developing new materials and coatings for biomedical and engineering applications—such as biocompatible materials, nanobiodevices, drug delivery vehicles, membranes for separation and purification, and bio-microelectromechanical systems.