Enhanced permeability and retention (EPR), and the (over-) expression of angiogenesis-related surface receptors are key features of tumor blood vessels. As a consequence, EPR-mediated passive and RGD-and NGR-based active tumor targeting have received considerable attention in the last couple of years. Using several different in vivo and ex vivo optical imaging techniques, we here visualized and quantified the benefit of RGD-and NGR-based vascular vs. EPR-mediated passive tumor targeting. This was done using ~10 nm-sized polymeric nanocarriers, which were either labeled with DY-676 (peptide-modified polymers) or with DY-750 (peptide-free polymers). Upon co-injection into mice bearing both highly leaky CT26 and poorly leaky BxPC3 tumors, it was found that vascular targeting did work, resulting in rapid and efficient early binding to tumor blood vessels, but that over time, passive targeting was significantly more efficient, leading to higher overall levels and to more efficient retention within tumors. Although this situation might be different for larger carrier materials, these insights indicate that caution should be taken not to over-estimate the potential of active over passive tumor targeting. KeywordsNanomedicine; Drug targeting; EPR; RGD; NGR Paralleled by the ever-increasing advances in nanotechnology and chemical engineering, nanomedicine formulations have started to attract significant attention in the last couple of years. Nanomedicines are 1-100(0) nm-sized carrier materials designed to improve the biodistribution and target site accumulation of low-molecular-weight (chemo-) therapeutic agents. By means of both passive and active targeting mechanisms, nanocarrier materials * Corresponding Authors Prof. Dr. Fabian Kiessling; Tel: +49-241-8080116; fkiessling@ukaachen.de Dr. Dr. Twan Lammers; Tel: +49-241-8036681; tlammers@ukaachen.de. Supporting Information Materials and methods describing the synthesis and characterization of the polymeric nanocarriers are provided as supplementary information. This material is available free of charge via the Internet at http://pubs.acs.org. Europe PMC Funders GroupAuthor Manuscript Nano Lett. Author manuscript; available in PMC 2014 March 04. Published in final edited form as:Nano Lett. 2014 February 12; 14(2): 972-981. doi:10.1021/nl404391r. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts aim to more efficiently deliver drug molecules to pathological sites, while at the same time preventing their accumulation in potentially endangered healthy tissues, thereby beneficially affecting the balance between their efficacy and toxicity 1-4 .Passive drug targeting relies on the hyper-permeable tumor vasculature. Endothelial gaps and improperly aligned vascular endothelium result in leaky blood vessels, which enable the extravasation of carrier materials with sizes of up to several 100's of nm into the tumor interstitium. In addition to this, dysfunctional lymphatic drainage results in the retention of extravasated nanomaterials within tumo...

Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist ® and Sinerem ®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications.

The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC) with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential) which was found to be favorable for bone regeneration and osseointegration of dental implants.

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