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The synthesis of microcapsules consisting of DNA shells crosslinked by anti-VEGF (vascular epithelial growth factor) or anti-ATP (adenosine triphosphate) aptamers and loaded with tetramethylrhodamine-modified dextran, TMR-D, and Texas Red-modified dextran, TR-D, respectively, as fluorescence labels acting as models for drug loads, is described. The aptamer-functionalized microcapsules act as stimuli-responsive carriers for the triggered release of the fluorescent labels in the presence of the overexpressed cancer cell biomarkers VEGF or ATP. The VEGF- and ATP-responsive microcapsules are, also, loaded with the anticancer drug doxorubicin (DOX), in the form of DOX-functionalized dextran, DOX-D. The release of DOX-D from the respective microcapsules proceeds in the presence of VEGF or ATP as triggers. Preliminary cell experiments reveal that the ATP-responsive DOX-D-loaded microcapsules undergo effective endocytosis into MDA-MB-231 cancer cells. The ATP-responsive DOX-D-loaded microcapsules incorporated into the MDA-MB-231 cancer cells reveal impressive cytotoxicity as compared to normal epithelial MCF-10A breast cells (50% vs 0% cell death after 24 h, respectively). The cytotoxicity of the ATP-responsive DOX-D-loaded microcapsules toward the cancer cells is attributed to the effective unlocking of the microcapsules by overexpressed ATP, and to the subsequent release of DOX from the dextran backbone under acidic conditions present in cancer cells (pH = 6.2). [ABSTRACT FROM AUTHOR]

Cancer is one of the leading non-communicable diseases with highest mortality rates worldwide. About half of all cancer patients receive radiation treatment in the course of their disease. However, treatment outcome and curative potential of radiotherapy is often impeded by genetically and/or environmentally driven mechanisms of tumor radioresistance and normal tissue radiotoxicity. While nanomedicine-based tools for imaging, dosimetry and treatment are potential keys to the improvement of therapeutic efficacy and reducing side effects, radiotherapy is an established technique to eradicate the tumor cells. In order to progress the introduction of nanoparticles in radiooncology, due to the highly interdisciplinary nature, expertise in chemistry, radiobiology and translational research is needed. In this report recent insights and promising policies to design nanotechnology-based therapeutics for tumor radiosensitization will be discussed. An attempt is made to cover the entire field from preclinical development to clinical studies. Hence, this report illustrates (1) the radio- and tumor-biological rationales for combining nanostructures with radiotherapy, (2) tumor-site targeting strategies and mechanisms of cellular uptake, (3) biological response hypotheses for new nanomaterials of interest, and (4) challenges to translate the research findings into clinical trials. [ABSTRACT FROM AUTHOR]

Labeled nanoparticles have attracted much interest toward applications in bioimaging and diagnostics. In particular, surface enhanced Raman scattering (SERS) nanotags have been demonstrated to be excellent candidates for multiplexed imaging and biological detection. We propose an alternative, effective method to easily prepare gold nanostars exhibiting plasmon bands in the near-infrared range, encoded with Raman reporter molecules, concomitantly acting as capping agents which are then protected with an amphiphilic polymer. The resulting nanotags are noncytotoxic and display long-term stability against aggregation and reporter leakage, while showing reproducible SERS signals suitable for multiplexing. These tags were used to distinguish five different types of breast cancer cells by imaging of a quintuple cell coculture. Time-lapse SERS imaging of the coculture was additionally performed, demonstrating the applicability of these nanotags for cell tracing over time scales above 24 h. [ABSTRACT FROM AUTHOR]