Multifunctional and robust composite materials comprising gold nanoparticles at a spherical polystyrene particle surface

The preparation of composite particles comprising gold nanoparticles (4.5–26 nm) assembled at a polystyrene (PS) surface with tunable loading is reported with wide ranging potentials from cellular studies to catalysis.</p

Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells

Who wants to be involved in health care decisions? Comparing preferences for individual and collective involvement in England and Sweden

Background: Patient and public involvement (PPI) is framed as positive for individuals, the health system, public health, as well as for communities and society as a whole. We investigated whether preferences for PPI differed between two countries with Beveridge type health systems-Sweden and England. We measured willingness to be involved in individual treatment decisions and in decisions about the organization and provision of local health and social care services. Methods: This was a comparative cross-sectional study of the general population's preferences. Together, the two samples included 3125 respondents; 1625 in England and 1500 in Sweden. Country differences were analysed in a multinomial regression model controlling for gender, age and educational attainment. Results: Overall, 68% of respondents wanted a passive patient role and 44% wanted to be involved in local decisions about organization and provision of services. In comparison with in Sweden, they were in England less likely to want a health professional such as a GP or consultant to make decisions about their treatment and also more likely to want to make their own decisions. They were also less likely to want to be involved in local service development decisions. An increased likelihood of wanting to be involved in organizational decision-making was associated with individuals wanting to make their own treatment decisions. Women were less likely to want health professionals to make decisions and more likely to want to be involved in organizational decisions. Conclusions: An effective health system that ensures public health must integrate an effective approach to PPI both in individual treatment decisions and shaping local health and social care priorities. To be effective, involvement activities must take in to account the variation in the desire for involvement and the implications that this has for equity. More work is needed to understand the relationship between the desire to be involved and actually being involved, but both appear related to judgements of the impact of involvement on health care decisions

Systemic RALA/iNOS nanoparticles; a potent gene therapy for metastatic breast cancer coupled as a biomarker of treatment

This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60 nm in diameter with a charge of 25 mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident. Nanoparticles harboring iNOS plasmids (constitutively active cytomegalovirus [CMV]-driven or transcriptionally regulated human osteocalcin [hOC]-driven) evoked iNOS protein expression and nitrite accumulation and impaired clonogenicity in the highly aggressive MDA-MB-231 human breast cancer model. Micrometastases of MDA-MB-231-luc-D3H1 cells were established in female BALB/c SCID mice by intracardiac delivery. Nanoparticulate RALA/CMV-iNOS or RALA/hOC-iNOS increased median survival in mice bearing micrometastases by 27% compared with controls and also provoked elevated blood nitrite levels. Additionally, iNOS gene therapy sensitized MDA-MB-231-luc-D3H1 tumors to docetaxel treatment. Studies demonstrated that systemically delivered RALA-iNOS nanoparticles have therapeutic potential for the treatment of metastatic breast cancer. Furthermore, detection of nitrite levels in the blood serves as a reliable biomarker of treatment. Keywords: nonviral gene therapy, nitric oxide, nanoparticle, breast cancer, metastasi

Preclincial evaluation of Gold-DTDTPA Nanoparticles As Theranostic Agents In Prostate Cancer Radiotherapy

International audienceAim: Gold nanoparticles have attracted significant interest in cancer diagnosis and treatment. Herein, we evaluated the theranostic potential of dithiolated diethylenetriamine pentaacetic acid (DTDTPA) conjugated AuNPs (Au@DTDTPA) for CT-contrast enhancement and radiosensitization in prostate cancer. Materials & methods: In vitro assays determined Au@DTDTPA uptake, cytotoxicity, radiosensitizing potential and DNA damage profiles. Human PC3 xenograft tumor models were used to determine CT enhancement and radiation modulating effects in vivo. Results: Cells exposed to nanoparticles and radiation observed significant additional reduction in survival compared with radiation only. Au@DTDTPA produced a CT enhancement of 10% and a significant extension in tumor growth delay from 16.9 days to 38.3 compared with radiation only. Conclusion: This study demonstrates the potential of Au@DTDTPA to enhance CT-image contrast and simultaneously increases the radiosensitivity of prostate tumors

Double-Peaked Balmer Emission Indicating Prompt Accretion Disk Formation in an X-Ray Faint Tidal Disruption Event

We present the multi-wavelength analysis of the tidal disruption event (TDE) AT~2018hyz (ASASSN-18zj). From follow-up optical spectroscopy, we detect the first unambiguous case of resolved double-peaked Balmer emission in a TDE. The distinct line profile can be well-modelled by a low eccentricity ($e\approx0.1$) accretion disk extending out to $\sim$100 $R_{p}$ and a Gaussian component originating from non-disk clouds, though a bipolar outflow origin cannot be completely ruled out. Our analysis indicates that in AT~2018hyz, disk formation took place promptly after the most-bound debris returned to pericenter, which we estimate to be roughly tens of days before the first detection. Redistribution of angular momentum and mass transport, possibly through shocks, must occur on the observed timescale of about a month to create the large \Ha-emitting disk that comprises $\lesssim$5\% of the initial stellar mass. With these new insights from AT~2018hyz, we infer that circularization is efficient in at least some, if not all optically-bright, X-ray faint TDEs. In these efficiently circularized TDEs, the detection of double-peaked emission depends on the disk inclination angle and the relative strength of the disk contribution to the non-disk component, possibly explaining the diversity seen in the current sample.Comment: 24 pages, 8 figures, 6 tables. Accepted for publication in Ap

Landsat 9 Thermal Infrared Sensor 2 Architecture and Design

The Thermal Infrared Sensor 2 (TIRS-2) will fly aboard the Landsat 9 spacecraft and leverages the Thermal Infrared Sensor (TIRS) design currently flying on Landsat 8. TIRS-2 will provide similar science data as TIRS, but is not a buildto-print rebuild due to changes in requirements and improvements in absolute accuracy. The heritage TIRS design has been modified to reduce the influence of stray light and to add redundancy for higher reliability over a longer mission life. The TIRS-2 development context differs from the TIRS scenario, adding to the changes. The TIRS-2 team has also learned some lessons along the way