Showing papers by "Gert Storm published in 2009"

Superparamagnetic iron oxide nanoparticles encapsulated in biodegradable thermosensitive polymeric micelles: toward a targeted nanomedicine suitable for image-guided drug delivery.

Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been receiving great attention lately due to their various biomedical applications, such as in MR imaging and image guided drug delivery. However, their systemic administration still remains a challenge. In this study, the ability of biodegradable thermosensitive polymeric micelles to stably encapsulate hydrophobic oleic-acid-coated SPIONs (diameter 5−10 nm) was investigated, to result in a system fulfilling the requirements for systemic administration. The micelles were composed of amphiphilic, thermosensitive, and biodegradable block copolymers of poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide dilactate] (mPEG-b-p(HPMAm-Lac2)). The encapsulation was performed by addition of one volume of SPIONs in THF to nine volumes of a cold aqueous mPEG-b-p(HPMAm-Lac2) solution (0 °C; below the cloud point of the polymer), followed by rapid heating of the resulting mixture to 50 °C, to induce micelle formation (“rapid heating” procedure). Dynam...

Crosstalk between epidermal growth factor receptor- and insulin-like growth factor-1 receptor signaling: implications for cancer therapy

Abstract: Both the epidermal growth factor receptor (EGFR) and the insulin-like growth factor-1 receptor (IGF-1R) can contribute to tumor development and -progression through their effects on cell proliferation, inhibition of apoptosis, angiogenesis, anchorage-independent growth and tumor-associated inflammation. EGFR-targeting monoclonal antibodies and small molecule tyrosine kinase inhibitors are currently in clinical use for the treatment of several types of cancer. However, primary and acquired resistance to these agents often occurs and thereby limits the clinical efficacy of mono-specific targeted therapy. Results from both in vitro and in vivo studies indicate that cross-talk between EGFR and IGF-1R can lead to acquired resistance against EGFR-targeted drugs. This review describes the interface between the EGFR and IGF-1R signaling networks and the implications of the extensive cross-talk between these two receptor systems for cancer therapy. EGFR and IGF-1R interact on multiple levels, either through a direct association between the two receptors, by mediating the availability of each others ligands, or indirectly, via common interaction partners such as G protein coupled receptors (GPCR) or downstream signaling molecules. This multi-layered cross-talk and its involvement in the induction of resistance to targeted therapies provide a clear rationale for dual targeting of EGFR and IGF-1R. We discuss several (potential) strategies to simultaneously inhibit EGFR and IGF-1R signaling as promising novel therapeutic approaches.

Molecular imaging of tumor angiogenesis using αvβ3-integrin targeted multimodal quantum dots

Abstract: Molecular imaging of angiogenesis is urgently needed for diagnostic purposes such as early detection, monitoring of (angiostatic) therapy and individualized therapy. Multimodality molecular imaging is a promising and refined technique to study tumor angiogenesis, which has so far been largely unexplored due to the lack of suitable multimodal contrast agents. Here, we report on the application of a novel αvβ3-specific quantum dot-based nanoparticle, which has been optimized for both optical and magnetic resonance detection of tumor angiogenesis. Upon intravenous injection of RGD-pQDs in tumor-bearing mice, intravital microscopy allowed the detection of angiogenically activated endothelium at cellular resolution with a small scanning window and limited penetration depth, while magnetic resonance imaging was used to visualize angiogenesis at anatomical resolution throughout the entire tumor. Fluorescence imaging allowed whole-body investigation of angiogenic activity. Using these quantum dots and the aforementioned imaging modalities, the angiogenic tumor vasculature was readily detected with the highest angiogenic activity occurring in the periphery of the tumor. This nanoparticle may be employed for multimodality imaging of a variety of diseases that are accompanied by activation of endothelial cells. Furthermore, the current technology might be developed for molecular imaging of other pathophysiological processes.

Synthetic vehicles for DNA vaccination.

Abstract: DNA vaccination is an attractive immunization method able to induce robust cellular immune responses in pre-clinical models. However, clinical DNA vaccination trials performed thus far have resulted in marginal responses. Consequently, strategies are currently under development to improve the efficacy of DNA vaccines. A promising strategy is the use of synthetic particle formulations as carrier systems for DNA vaccines. This review discusses commonly used synthetic carriers for DNA vaccination and provides an overview of in vivo studies that use this strategy. Future recommendations on particle characteristics, target cell types and evaluation models are suggested for the potential improvement of current and novel particle delivery systems. Finally, hurdles which need to be tackled for clinical evaluation of these systems are discussed.

Targeted delivery of anti-inflammatory agents to tumors.

Abstract: Inflammation is considered a hallmark of cancer. The chronic inflammatory process is driven by the interaction of cells, proteins, cytokines, transcription factors, and lipid mediators within the tumor microenvironment giving rise to complex pro-inflammatory cascades. These can be inhibited by a variety of different anti-inflammatory compounds, like non-steroidal anti-inflammatory drugs, glucocorticoids, anti-inflammatory biologicals, phytotherapeutics (mainly polyphenols), and drugs with pleiotropic anti-inflammatory effects. In general, it appears that the anti-tumor activity of these compounds occurs at higher doses than the doses used in conventional anti-inflammatory therapy. To optimally take advantage of the anti-tumor activity and at the same time limit side effects, targeted delivery of anti-inflammatory drugs appears an attractive approach.