Band 7, Heft 4

Theranostics are a multifunctional approach using nanoparticles for combined diagnostic and therapeutic purposes. The hybrid nanoparticles that are applied for these purposes are composed of an inorganic core and an organic shell. The inorganic core acts as a contrast enhancer and the organic shell acts as a drug releaser. Hybrid nanoparticles can be conjugated with targeting moieties and systematically administered to patients to direct the nanoparticles to specific cells such as cancer cells. Theranostics have the potential to significantly improve early stage cancer diagnostics and patient survival. This review discusses preclinical and clinical advances in applications of inorganic nanoparticles for the theranostics of cancer.

To explore the role of complement (C) activation in the hypersensitivity reactions (HSRs) to some anticancer drugs, as well as the use of the C activation biomarkers (C biom ) C3a, C5a and SC5b-9 in the prediction of HSRs, we measured these C biom in plasma samples of cancer patients during infusion therapy, and in their pretreatment (screening) serum incubated with these drugs in vitro. Rituximab and paclitaxel caused mild to severe HSRs in 8/20 and 4/4 patients, respectively, which were associated with rises or falls of plasma and/or serum C bioms . Among these changes, a rise of C3a in the plasma of 8/8 rituximab reactors and strong rises of C bioms in the screening sera of all paclitaxel patents were most prominent. However, in the case of rituximab, significant C biom changes were also seen in nonreactors, while C biom changes were absent in the screening serum. Thus, C activation may be causally involved, but it is not rate limiting factor to HSRs to rituximab. Additional initial data in this study suggest that a whole blood assay using hirudin is more sensitive to C activation by rituximab than the serum test; that trastuzumab and docetaxel also cause HSRs with changes of C bioms , and that an anti-paclitaxel antibody (ADA) ELISA may be useful as a predictor test for HSRs to Paclitaxel.

The physico-chemical characterization of novel celecoxib-loaded beta-casein micelles (Cx/bCN) was recently described and its superiority in enhancing celecoxib bioavailability after intraduodenal administration to pigs was demonstrated. Here, using solution differential scanning calorimetry (DSC) combined with analysis of size distribution by DLS, zeta potential and changes in composition we demonstrate that the above superiority may be related to the thermotropic behavior of these micelles under physiological conditions. DSC of Cx/bCN reveals a characteristic irreversible exotherm upon heating, having its temperature of maximal change in heat capacity (T m ) at 40–46°C, depending on the Cx/bCN ratio. The higher the Cx/bCN ratio, the lower is T m . While the thermodynamically stable bCN (alone) micelles lack any phase transition, the heat-induced, irreversible structural change of Cx/bCN micelles was associated with almost complete drug release, while micelle diameter and zeta potential decreased. Heating drug-free bCN micelles was effect-less. Altogether, our results suggest that Cx/bCN micelles are metastable supramolecular assemblies that transform upon heating to thermodynamically stable drug-free bCN micelles while releasing their drug-load. These findings also indicate the utility of DSC for future development of bCN micelles as nano-drugs, as well as of other supramolecular-assembly nano-drugs.

In this paper, it aims to build the relationship of statically electric interaction between the surface charge of a particle drug and cellular uptake. The statically electric theory is applied to study the change of wetting between the drug particle and the cell, a factor that enhanced uptake of cells induced by particle’s surface charge is introduced, then it is formulated according to Kelvin theory for dissolving of solid particle in liquid. It is found that the change of contact angle between the surface charged particle drug and the cell can be detected if the Zeta potential reaches to 6 mV in water like solution, an increase of about 11.1% for the uptake could be obtained for a polymer particle with molar mass M ∼10 kg/mol, mass density ρ ∼0.9×10 3 kg/m 3 , radius r ∼15 nm at temperature 300 K and Zeta potential 10 mV condition as compared with the same particle in water-like solution but without surface charge. The effect of particle surface charge on drug uptake could be interpreted by statically electric theory.