No abstract

Our ability to engineer nanomaterials for biological and medical applications is continuously increasing, and nanomaterial designs are becoming more and more complex. One very good example of this is the drug delivery field where nanoparticle systems can be used to deliver drugs specifically to diseased tissue. In the early days, the design of the nanoparticles was relatively simple, but today we can surface functionalize and manipulate material properties to target diseased tissue and build highly complex drug release mechanisms into our designs. One of the most promising strategies in drug delivery is to use ligands that target overexpressed or selectively expressed receptors on the surface of diseased cells. To utilize this approach, it is necessary to control the chemistry involved in surface functionalization of nanoparticles and construct highly specific functionalities that can be used as attachment points for a diverse range of targeting ligands such as antibodies, peptides, carbohydrates and vitamins. In this review we provide an overview and a critical evaluation of the many strategies that have been developed for surface functionalization of nanoparticles and furthermore provide an overview of how these methods have been used in drug delivery systems.

We present here a highly efficient and chemoselective liposome functionalization method based on oxime bond formation between a hydroxylamine and an aldehyde-modified lipid component. We have conducted a systematic and quantitative comparison of this new approach with other state-of-the-art conjugation reactions in the field. Targeted liposomes that recognize overexpressed receptors or antigens on diseased cells have great potential in therapeutic and diagnostic applications. However, chemical modifications of nanoparticle surfaces by postfunctionalization approaches are less effective than in solution and often not high-yielding. In addition, the conjugation efficiency is often challenging to characterize and therefore not addressed in many reports. We present here an investigation of PEGylated liposomes functionalized with a neuroendocrine tumor targeting peptide (TATE), synthesized with a variety of functionalities that have been used for surface conjugation of nanoparticles. The reaction kinetics and overall yield were quantified by HPLC. Reactions were conducted in solution as well as by postfunctionalization of liposomes in order to study the effects of steric hindrance and possible affinity between the peptide and the liposome surface. These studies demonstrate the importance of choosing the correct chemistry in order to obtain a quantitative surface functionalization of liposomes.

External beam radiation therapy relies on the ability to deliver high radiation doses to tumor cells with minimal exposure to surrounding healthy tissue. Advanced irradiation techniques, including image-guided radiation therapy (IGRT), rely on the ability to locate tumors to optimize the therapeutic benefit of these techniques. Today, radiopaque fiducial tissue markers are placed in or around tumors, for example, in prostate cancer patients to enhance the precision of daily and/or real-time IGRT. A liquid injectable fiducial marker (nanogel) is developed based on PEGylated gold nanoparticles and sucrose acetate isobutyrate (SAIB) with improved properties compared to current solid fiducial markers. The developed nanogel is investigated in vitro and subsequently evaluated in vivo in immunocompetent NMRI mice. The nanogel shows high CT-contrast and excellent stability in vivo over a period of 12 weeks. The nanogel is found to be biocompatible and well tolerated. No induction of the inflammatory cytokines INF-γ, IL-6, or TNF-α is observed throughout the study period. The developed nanogel seems to be a safe injectable fiducial marker ideally suited for IGRT that may further enhance the effect of radiation.