Clinical relevance of the expression of somatostatin receptors in digestive endocrine tumours
II Medical School Sapienza University of Rome, Sant'Andrea Hospital, Italy.Digestive and Liver Disease (Impact Factor: 2.96). 03/2010; 42(3):173-4. DOI: 10.1016/j.dld.2009.12.009
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ABSTRACT: For drug development and quality monitoring targeted at somatostatin (SST), a sensitive and reliable method is needed to detect the binding of somatostatins (SSTs) to their receptors - somatostatin receptors (SSTRs). In this study, interactions between SSTs (SST14, SST28) and SSTRs (SSTR2, SSTR4) have been measured by using surface plasmon resonance (SPR). SSTRs were covalently immobilized on the surfaces of the CM5 sensor chip via amine coupling and SSTs were injected into the flow channels. The results revealed that SST14 bound to SSTR4 with a much higher affinity than to SSTR2. Meanwhile, SST28 bound to SSTR4 with a slightly higher affinity when compared to SSTR2. SST14 and SST28 interacted with SSTR2 with a similar affinity, but SST14 had a relatively higher affinity of interaction with SSTR4 when compared to SST28. Furthermore, our study demonstrated that SSTR2-CM5 is capable of quantitating SST14 and SST28 with a detection range of 5 μg mL−1 to 50 μg mL−1 and 5 μg mL−1 to 40 μg mL−1, respectively. Therefore, the SPR technique not only offers a potentially sensitive and reproducible method for SSTR-selective drug discovery, but also might provide a rapid and quantitative bioassay for monitoring manufactural batch consistency.
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ABSTRACT: Abstract In this study, DOX-loaded supramolecular nanocarrier (DLSC) was assembled by using two new amphiphilic polymers, octreotide-polyethylene glycol monostearate (OPMS) and N-octyl-N-succinyl O-carboxymethyl chitosan (OSCC). The characteristics of the DLSC were investigated. The results indicated that the significant pH-triggered release in vitro. The cellular uptake of DLSC was much higher than that of DOX-loaded OSCC micelles (DLOM) in the SMMC-7721 (somatostatin receptor (SSTR) over-expressed cell) cells, which suggested the SSTR-mediated properties. A considerable amount of drug entered the nucleus due to the pH-triggered deformation of the supramolecular structure and rapid release of drug in acidic endosomes of tumor cells. The killing efficacy was much higher than that of DLOM in the SMMC-7721. In S180 sarcoma-bearing KM mice, the biodistribution and therapeutic activity were studied. DLSC showed extended circulation time in plasma, decreasing drug concentrations in the heart and accumulating drug concentrations in the pancreas and tumor. In addition, minimized weight changes and cardiac toxicity, high suppression ratio of tumor growth and longer survival time were observed after intravenous injection of DLSC. The studies suggested that the supramolecular nanocarrier constructed of different designated polymers with multiple functions would be one of the most effective approaches for active targeting drug delivery.
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