Cells as delivery vehicles for cancer therapeutics

Cell-based therapeutics have advanced significantly over the past decade and are poised to become a major pillar of modern medicine. Three cell types in particular have been studied in detail for their ability to home to tumors and to deliver a variety of different payloads. Neural stem cells, mesenchymal stem cells and monocytes have each been shown to have great potential as future delivery systems for cancer therapy. A variety of other cell types have also been studied. These results demonstrate that the field of cell-based therapeutics will only continue to grow

Nanoscopic surfactant behavior of the porin MspA in aqueous media

The mycobacterial porin MspA is one of the most stable channel proteins known to date. MspA forms vesicles at low concentrations in aqueous buffers. Evidence from dynamic light scattering, transmission electron microscopy and zeta-potential measurements by electrophoretic light scattering indicate that MspA behaves like a nanoscale surfactant. The extreme thermostability of MspA allows these investigations to be carried out at temperatures as high as 343 K, at which most other proteins would quickly denature. The principles of vesicle formation of MspA as a function of temperature and the underlying thermodynamic factors are discussed here. The results obtained provide crucial evidence in support of the hypothesis that, during vesicle formation, nanoscopic surfactant molecules, such as MspA, deviate from the principles underlined in classical surface chemistry

A hybrid soft solar cell based on the mycobacterial porin MspA linked to a sensitizer-viologen diad

A prototype of a nano solar cell containing the mycobacterial channel protein MspA has been successfully designed. MspA, an octameric transmembrane channel protein from Mycobacterium smegmatis, is one of the most stable proteins known to date. Eight Ruthenium(II) aminophenanthroline-viologen maleimide Diads (Ru-Diads) have been successfully bound to the MspA mutant MspAA96C via cysteine-maleimide bonds. MspA is known to form double layers in which it acts as nanoscopic surfactant. The nanostructured layer that is formed by (Ru-Diad)(8)MspA at the TiO2 electrode is photochemically active. The resulting "protein nano solar cell" features an incident photon conversion efficiency of 1% at 400 nm. This can be regarded as a proof-of-principle that stable proteins can be successfully integrated into the design of solar cells

Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle

Citation: Wendel, S. O., Menon, S., Alshetaiwi, H., Shrestha, T. B., Chlebanowski, L., Hsu, W. W., . . . Troyer, D. L. (2015). Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle. Plos One, 10(5), 13. doi:10.1371/journal.pone.0128144The recent WHO report on antibiotic resistances shows a dramatic increase of microbial resistance against antibiotics. With only a few new antibiotics in the pipeline, a different drug delivery approach is urgently needed. We have obtained evidence demonstrating the effectiveness of a cell based drug delivery system that utilizes the innate immune system as targeting carrier for antibacterial drugs. In this study we show the efficient loading of neutrophil granulocytes with chlorhexidine and the complete killing of E. coli as well as Fusobacterium necrophorum in in-vitro studies. Fusobacterium necrophorum causes hepatic abscesses in cattle fed high grain diets. We also show in a mouse model that this delivery system targets infections of F. necrophorum in the liver and reduces the bacterial burden by an order of magnitude from approximately 2.10(6) to 1.10(5)

Iron-based magnetic nanosystems for diagnostic imaging and drug delivery : towards transformative biomedical applications

The advancement of biomedicine in a socioeconomically sustainable manner while achieving efficient patient-care is imperative to the health and well-being of society. Magnetic systems consisting of iron based nanosized components have gained prominence among researchers in a multitude of biomedical applications. This review focuses on recent trends in the areas of diagnostic imaging and drug delivery that have benefited from iron-incorporated nanosystems, especially in cancer treatment, diagnosis and wound care applications. Discussion on imaging will emphasise on developments in MRI technology and hyperthermia based diagnosis, while advanced material synthesis and targeted, triggered transport will be the focus for drug delivery. Insights onto the challenges in transforming these technologies into day-to-day applications will also be explored with perceptions onto potential for patient-centred healthcare

Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

Citation: Udukala, D. N., Wang, H. W., Wendel, S. O., Malalasekera, A. P., Samarakoon, T. N., Yapa, A. S., . . . Bossmann, S. H. (2016). Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection. Beilstein Journal of Nanotechnology, 7, 364-373. doi:10.3762/bjnano.7.33Additional Authors: Ortega, R.;Toledo, Y.;Bossmann, L.;Robinson, C.;Janik, K. E.;Koper, O. B.;Motamedi, M.;Zhu, G. H.Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl) porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis

Magnetic Nanomaterials for Magnetically-Aided Drug Delivery and Hyperthermia

Magnetic nanoparticles have continuously gained importance for the purpose of magnetically-aided drug-delivery, magnetofection, and hyperthermia. We have summarized significant experimental approaches, as well as their advantages and disadvantages with respect to future clinical translation. This field is alive and well and promises meaningful contributions to the development of novel cancer therapies