Nanoparticle Delivery: Targeting and Nonspecific Binding
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Generating Particles with Minimal Nonspecific Binding
Delivery: Targeting and Nonspecific Binding
Rihe Liu, Brian K. Kay, Shaoyi Jiang, and Shengfu Chen Abstract 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.
Introduction Many different types of molecules have been attached to the surface of nanoparticles for therapeutic applications. In one case, the coating molecules serve to minimize nonspecific adsorption to each other or to tissues in the body. Such a coating might consist of poly(ethylene glycol) (PEG), which is effective in prolonging the circulatory time by increasing the hydrodynamic size and also minimizing nonspecific adsorption due to its highly hydrophilic nature. In another case, the coating molecules serve to direct binding to the surface of specific cells, extracellular parts of tissue, or organs. In addition, the coating molecules can play a role in cell uptake. Since the nanoparticles are relatively simple in composition, the binding and uptake functions are supplied by “smart molecules” or “target-capturing reagents” that the investigator attaches in 432
a variety of manners, without loss in their targeting functions, to the surface of the nanoparticles. Generally speaking, a capturing molecule with a higher targetbinding affinity is expected to have better performance and advantages in most instances, including overcoming numerous transport barriers to direct nanoparticles to reach cancer cells, despite the potential “binding site barrier” caused by antibody-binding molecules (antigen) located at the periphery of the tumor.1,2 Various smart molecules have been developed and used to conjugate with nanoparticles to achieve active targeting, including those that consist of chemical moieties of peptides, antibodies, engineered p
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