Multifunctional nanoparticle-EpCAM aptamer bioconjugates: a paradigm for targeted drug delivery and imaging in cancer therapy

The promising proposition of multifunctional nanoparticles for cancer diagnostics and therapeutics has inspired the development of theranostic approach for improved cancer therapy. Moreover, active targeting of drug carrier to specific target site is crucial for providing efficient delivery of therapeutics and imaging agents. In this regard, the present study investigates the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles, functionalized with a targeting ligand (EpCAM aptamer) and an imaging agent (quantum dots) for cancer therapy and bioimaging. A wide spectrum of in vitro analysis (cellular uptake study, cytotoxicity assay, cell cycle and apoptosis analysis, apoptosis associated proteins study) revealed superior therapeutic potentiality of targeted drug loaded NPs over other formulations in EpCAM expressing cells. Moreover, our nanotheranostic system served as a superlative bio-imaging modality both in 2D monolayer culture and tumor spheroid model. Our result suggests that, these aptamer-guided multifunctional NPs may act as indispensable nanotheranostic approach toward cancer therapy.

Using patients' experiences of adverse events to improve health service delivery and practice: protocol of a data linkage study of Australian adults age 45 and above

Evidence of patients' experiences is fundamental to creating effective health policy and service responses, yet is missing from our knowledge of adverse events. This protocol describes explorative research redressing this significant deficit; investigating the experiences of a large cohort of recently hospitalised patients aged 45 years and above in hospitals in New South Wales (NSW), Australia.

Optimizing delivery of recovery-oriented online self-management strategies for bipolar disorder : a review

Self-management is emerging as a viable alternative to difficult-to-access psychosocial treatments for bipolar disorder (BD), and has particular relevance to recovery-related goals around empowerment and personal meaning. This review examines data and theory on BD self-management from a recovery-oriented perspective, with a particular focus on optimizing low-intensity delivery of self-management tools via the web.

Fabrication of high specificity hollow mesoporous silica nanoparticles assisted by Eudragit for targeted drug delivery.

Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising carriers for effective drug delivery due to their large surface area, high volume for drug loading and excellent biocompatibility. However, the non-ionic surfactant templated HMSNs often have a broad size distribution and a defective mesoporous structure because of the difficulties involved in controlling the formation and organization of micelles for the growth of silica framework. In this paper, a novel "Eudragit assisted" strategy has been developed to fabricate HMSNs by utilising the Eudragit nanoparticles as cores and to assist in the self-assembly of micelle organisation. Highly dispersed mesoporous silica spheres with intact hollow interiors and through pores on the shell were fabricated. The HMSNs have a high surface area (670m(2)/g), small diameter (120nm) and uniform pore size (2.5nm) that facilitated the effective encapsulation of 5-fluorouracil within HMSNs, achieving a high loading capacity of 194.5mg(5-FU)/g(HMSNs). The HMSNs were non-cytotoxic to colorectal cancer cells SW480 and can be bioconjugated with Epidermal Growth Factor (EGF) for efficient and specific cell internalization. The high specificity and excellent targeting performance of EGF grafted HMSNs have demonstrated that they can become potential intracellular drug delivery vehicles for colorectal cancers via EGF-EGFR interaction.

Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles.

Abstract The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC50 of 5.69 µg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC50 of 22.9 and 14.17 µg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.

miRNA modulation of SOCS1 using an influenza A virus delivery system

Difficulties associated with efficient delivery and targeting of miRNAs to cells is hampering the real world application of miRNA technology. This study utilized an influenza A-based delivery system to express miR-155 in order to knockdown SOCS1 mRNA. Using qPCR and dual luciferase technology we show that miR-155 delivery resulted in a significant increase in cellular miR-155 which facilitated a downregulation of SOCS1 gene expression and a functional increase in IL-6 and IFN-β cytokines.

Mental health service delivery : a profile of mental health non-government organisations in south-east Queensland, Australia.

Non-government organisations make a substantial contribution to the provision of mental health services; despite this, there has been little research and evaluation targeted at understanding the role played by these services within the community mental health sector. The aim of the present study was to examine the depth and breadth of services offered by these organisations in south-east Queensland, Australia, across five key aspects of reach and delivery.

Portfolio delivery approach to township sewage treatment facilities in China: a case study

 The wide need for sewage treatment facilities at the township level across China implies an emerging niche market for water and sanitation developers, investors and financiers. However this potential market is difficult to enter with traditional financing and delivery methods, because township sewage features small amount, volatile quantity, geographically scattering, immature fee charging system, weak affordability, and lack of capacities. A group of concession sewage treatment projects collectively implemented by a private company in the Changsha County of Hunan Province under the so called ‘Changsha Model’ provided innovative solutions. This cases study first examined the portfolio approach in terms of multiple delivery method integration, technology, and centralized control system, and evaluated the replicability of the new model. Practices and lessons learned from the case were then presented and summarized that can be applied to the following township sewage treatment facility development. Last, the Changsha Model was compared with similar infrastructure portfolio delivery solutions applied in the US.

An aptamer-mediated siRNA delivery system targeting breast tumourigenic cells

In this study, through developing a RNA interference based gene-knockdown system, the expression of Survivin - a critical gene involved in breast cancer initiation and relapse was silenced. This approach reversed chemo-resistance, transforming Doxorubicin - a classical chemotherapy drug to one able to act on drug-resistant breast cancer stem cells.

Nanostructured liquid crystalline particles as next generation agrochemical delivery vehicles

A new system for delivering agrichemicals to crop plants was investigated. Nano-structured lipid particles were used as an alternative to traditional surfactants for penetrating plant surfaces. In laboratory and field trials the nanoparticles delivered chemicals effectively, caused less damage to plants, required less water and resulted in lower environmental impacts.

Alternative service delivery models for families with a new speech generating device: perspectives of parents and therapists

Purpose: Research has revealed limitations in the provision of in-person services to families with a new speech generating device (SGD), both in Australia and overseas. Alternative service models such as parent training, peer support and telepractice may offer a solution, but their use with this population has not been researched to date.

Method: Using interviews and focus groups, this study explored the experiences and opinions of 13 speech-language pathologists and seven parents regarding alternatives to in-person support and training for families with a new SGD. Data were analysed using grounded theory. Themes explored in this paper include the benefits and drawbacks of alternative service models as well as participants’ suggestions for the optimal implementation of these approaches.

Result: Participants confirmed the utility of alternative service models, particularly for rural/remote and underserviced clients. Benefits of these models included reduced travel time for families and therapists, as well as enhanced information access, support and advocacy for parents.

Conclusion: Participants viewed the provision of ongoing professional support to families as critical, regardless of service modality. Additional issues arising from this study include the need for development of organizational policies, resources and training infrastructure to support the implementation of these alternative service models.

Exploring nurses' reactions to a novel technology to support acute health care delivery

AIMS AND OBJECTIVES: To explore nurses' reactions to new novel technology for acute health care. BACKGROUND: Past failures of technology developers to deliver products that meet nurses' needs have led to resistance and reluctance in the technology adoption process. Thus, involving nurses in a collaborative process from early conceptualisation serves to inform design reflective upon current clinical practice, facilitating the cementing of 'vision' and expectations of the technology. DESIGN: An exploratory descriptive design to capture nurses' immediate impressions. METHODS: Four focus groups (52 nurses from medical and surgical wards at two hospitals in Australia; one private and one public). RESULTS: Nursing reactions towards the new technology illustrated a variance in barrier and enabler comments across multiple domains of the Theoretical Domains Framework. Most challenging for nurses were the perceived threat to their clinical skill, and the potential capability of the novel technology to capture their clinical workflow. Enabling reactions included visions that this could help integrate care between departments; help management and support of nursing processes; and coordinating their patients care between clinicians. Nurses' reactions differed across hospital sites, influenced by their experiences of using technology. For example, Site 1 nurses reported wide variability in their distribution of barrier and enabling comments and nurses at Site 2, where technology was prevalent, reported mostly positive responses. CONCLUSION: This early involvement offered nursing input and facilitated understanding of the potential capabilities of novel technology to support nursing work, particularly the characteristics seen as potentially beneficial (enabling technology) and those conflicting (barrier technology) with the delivery of both safe and effective patient care. RELEVANCE TO CLINICAL PRACTICE: Collaborative involvement of nurses from the early conceptualisation of technology development brings benefits that increase the likelihood of successful use of a tool intended to support the delivery of safe and efficient patient care.