20 research outputs found
Nanoengineering liquid metal core–shell nanostructures
No full textNanoengineering the composition and morphology of functional nanoparticles endows them to perform multiple tasks and functions. An intriguing strategy for creating multifunctional nanomaterials involves the construction of core–shell nanostructures, which have enabled promising applications in biomedicine, energy, sensing, and catalysis. Here, a straightforward nanoengineering approach is presented utilizing liquid metal nanoparticles and galvanic replacement to create diverse core–shell nanostructures. Controlled nanostructures including liquid metal core-gold nanoparticle shell (LM@Au), gold nanoparticle core-gallium oxide shell (Au@Ga oxide), and hollow Ga oxide nanoparticles are successfully fabricated. Remarkably, these investigations reveal that LM@Au exhibits exceptional photothermal performance, achieving an impressive conversion efficiency of 65.9%, which is five times that of gold nanoparticles. By leveraging the high photothermal conversion efficiency and excellent biocompatibility of LM@Au, its promising application in hyperthermia cancer therapy is demonstrated. This simple yet powerful nanoengineering strategy opens new avenues for the controlled synthesis of complex core–shell nanostructures, advancing various fields beyond biomedicine.</p
Development and characterisation of star-shaped nanoparticles to deliver therapeutic siRNA to medulloblastoma
No full textBrain cancer kills more children in Australia than any other disease. Medulloblastoma (MB) accounts for approximately 20% of all childhood brain tumours. Chemoresistance, relapse and treatment related toxicity are common for this disease. There is an urgent need to develop new effective and less toxic treatments.
Gene therapies which use short-interfering RNA (siRNA) to silence the expression of a target gene have great potential for the treatment of a host of human diseases including cancer. However, a major hurdle for the clinical translation of siRNA drugs is the need for a delivery vehicle to allow siRNA to internalise into cells. Nanoparticles may offer a solution to this problem and can be used as delivery vehicles for siRNA. No studies have examined the potential of star nanoparticles for the treatment of MB.
The aims of this study were to: 1) define the biological conditions for di-block copolymer nanoparticles (star nanoparticles) to deliver siRNA to MB cells in vitro to silence the expression of a gene (Polo-Like Kinase 1, PLK1) which is highly expressed in MB cells and plays a major role in promoting tumour growth; 2) determine whether star nanoparticles could deliver siRNA to solid tumours in mice; and 3) examine whether Star nanoparticle-siRNA (star-siRNA) could penetrate a blood-brain barrier (BBB).
Results from this thesis demonstrate that star-siRNA form monodisperse nanoparticles with a size of 19 nm. Star-siRNA is internalised into MB cells in vitro and can silence PLK1 expression leading to mitotic arrest, DNA damage and apoptosis. Star-siRNA was non-toxic to mice and siRNA could be effectively delivered to subcutaneous MB tumours to silence PLK1 expression which induced apoptosis. Finally, using in vitro and in vivo models we showed that star-siRNA could penetrate the BBB. Importantly, star nanoparticles delivered siRNA to the brains of mice with growing orthotopic MB tumours.
Collectively, results presented in this thesis demonstrate for the first time the potential of star nanoparticles to deliver siRNA to induce apoptosis in MB cells in vitro and in vivo. Star-siRNA nanodrugs may be a novel therapeutic strategy to inhibit MB growth and increase patient survival
Tailored fluorosurfactants through controlled/living radical polymerization for highly stable microfluidic droplet generation
No full textDroplet-based microfluidics represents a disruptive technology in the field of chemistry and biology through the generation and manipulation of sub-microlitre droplets. To avoid droplet coalescence, fluoropolymer-based surfactants are commonly used to reduce the interfacial tension between two immiscible phases to stabilize droplet interfaces. However, the conventional preparation of fluorosurfactants involves multiple steps of conjugation reactions between fluorinated and hydrophilic segments to form multiple-block copolymers. In addition, synthesis of customized surfactants with tailored properties is challenging due to the complex synthesis process. Here, we report a highly efficient synthetic method that utilizes living radical polymerization (LRP) to produce fluorosurfactants with tailored functionalities. Compared to the commercialized surfactant, our surfactants outperform in thermal cycling for polymerase chain reaction (PCR) testing, and exhibit exceptional biocompatibility for cell and yeast culturing in a double-emulsion system. This breakthrough synthetic approach has the potential to revolutionize the field of droplet-based microfluidics by enabling the development of novel designs that generate droplets with superior stability and functionality for a wide range of applications.</p
Nanomaterial integrated 3D printing for biomedical applications
No full text3D printing technology, otherwise known as additive manufacturing, has provided a promising tool for manufacturing customized biomaterials for tissue engineering and regenerative medicine applications. A vast variety of biomaterials including metals, ceramics, polymers, and composites are currently being used as base materials in 3D printing. In recent years, nanomaterials have been incorporated into 3D printing polymers to fabricate innovative, versatile, multifunctional hybrid materials that can be used in many different applications within the biomedical field. This review focuses on recent advances in novel hybrid biomaterials composed of nanomaterials and 3D printing technologies for biomedical applications. Various nanomaterials including metal-based nanomaterials, metal-organic frameworks, upconversion nanoparticles, and lipid-based nanoparticles used for 3D printing are presented, with a summary of the mechanisms, functional properties, advantages, disadvantages, and applications in biomedical 3D printing. To finish, this review offers a perspective and discusses the challenges facing the further development of nanomaterials in biomedical 3D printing.</p
Smart Fluorosurfactant-Assisted Microfluidics Powered On-Demand Generation and Retrieval of Cell-Laden Microgels
No full textMicrofluidics have been widely employed as powerful tools to fabricate monodisperse, cell-laden hydrogel microdroplets with precise control for various biological applications, particularly in tissue engineering. While these systems enable high-throughput production of uniform microgel particles, the encapsulation and stabilization of water-in-oil hydrogel emulsions often require surfactants to reduce the surface tension of the microgel droplets. However, these surfactants must be removed with chemical demulsifiers to retrieve the cell-laden microgels for downstream applications, which often leads to toxic effects on the cells. Herein, a novel class of thermo-responsive “smart” surfactants is reported for on-demand demulsification of microfluidic droplets. These surfactants are synthesized by coupling perfluoropolyethers (PFPEs) with a thermo-responsive block of N-isopropylacrylamide (NIPAM) using reversible addition-fragmentation chain transfer (RAFT) polymerization. The resulting P(NIPAM)(n)-PFPE surfactants exhibited temperature-dependent amphiphilicity, enabling stabilization of water-in-oil droplets at low temperatures and destabilization at elevated temperatures. This approach offers a non-invasive and biocompatible method for microgel recovery without the need for harmful chemical demulsifiers or additional processing steps. The combination of precise control over surfactant properties and thermo-responsive behavior opens new avenues for developing smart, biocompatible emulsion systems for advanced droplet microfluidics applications in tissue engineering, drug delivery, and single-cell analysis.Xiangke Li, Helen Forgham, Qiuren Shen, Liwen Zhang, Christoph Meinert, Chun-Xia Zhao, Yiliang Lin, Dan Yuan, Thomas P. Davis, and Ruirui Qia
Keeping up with the COVID's—Could siRNA‐based antivirals be a part of the answer?
No full textCoronavirus disease 2019 (COVID‐19) is a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This deadly infection has resulted in more than 5.2 million deaths worldwide. The global rollout of COVID‐19 vaccines has without doubt saved countless lives by reducing the severity of symptoms for patients. However, as the virus continues to evolve, there is a risk that the vaccines and antiviral designed to target the infection will no longer be therapeutically viable. Furthermore, there remain fears over both the short and long‐term side effects of repeat exposure to currently available vaccines. In this review, we discuss the pros and cons of the vaccine rollout and promote the idea of a COVID medicinal toolbox made up of different antiviral treatment modalities, and present some of the latest therapeutic strategies that are being explored in this respect to try to combat the COVID‐19 virus and other COVID viruses that are predicted to follow. Lastly, we review current literature on the use of siRNA therapeutics as a way to remain adaptable and in tune with the ever‐evolving mutation rate of the COVID‐19 virus
The transcriptional co-repressor Runx1t1 is essential for MYCN-driven neuroblastoma tumorigenesis
No full textMYCN oncogene amplification is frequently observed in aggressive childhood neuroblastoma. Using an unbiased large-scale mutagenesis screen in neuroblastoma-prone transgenic mice, we identify a single germline point mutation in the transcriptional corepressor Runx1t1, which abolishes MYCN-driven tumorigenesis. This loss-of-function mutation disrupts a highly conserved zinc finger domain within Runx1t1. Deletion of one Runx1t1 allele in an independent Runx1t1 knockout mouse model is also sufficient to prevent MYCN-driven neuroblastoma development, and reverse ganglia hyperplasia, a known pre-requisite for tumorigenesis. Silencing RUNX1T1 in human neuroblastoma cells decreases colony formation in vitro, and inhibits tumor growth in vivo. Moreover, RUNX1T1 knockdown inhibits the viability of PAX3-FOXO1 fusion-driven rhabdomyosarcoma and MYC-driven small cell lung cancer cells. Despite the role of Runx1t1 in MYCN-driven tumorigenesis neither gene directly regulates the other. We show RUNX1T1 forms part of a transcriptional LSD1-CoREST3-HDAC repressive complex recruited by HAND2 to enhancer regions to regulate chromatin accessibility and cell-fate pathway genes.Jayne E. Murray, Emanuele Valli, Giorgio Milazzo, Chelsea Mayoh, Andrew J. Gifford, Jamie I. Fletcher, Chengyuan Xue, Nisitha Jayatilleke, Firoozeh Salehzadeh, Laura D. Gamble, Jourdin R. C. Rouaen, Daniel R. Carter, Helen Forgham, Eric O. Sekyere, Joanna Keating, Georgina Eden, Sophie Allan, Stephanie Alfred, Frances K. Kusuma, Ashleigh Clark, Hannah Webber, Amanda J. Russell, Antoine de Weck, Benjamin T. Kile, Martina Santulli, Piergiuseppe De Rosa, Emmy D. G. Fleuren, Weiman Gao, Lorna Wilkinson-White, Jason K. K. Low, Joel P. Mackay, Glenn M. Marshall, Douglas J. Hilton, Federico M. Giorgi, Jan Koster, Giovanni Perini, Michelle Haber, Murray D. Norri
Recent Advances in Single Fe-Based Nanoagents for Photothermal–Chemodynamic Cancer Therapy
No full textMonomodal cancer therapies are often unsatisfactory, leading to suboptimal treatment effects that result in either an inability to stop growth and metastasis or prevent relapse. Thus, synergistic strategies that combine different therapeutic modalities to improve performance have become the new research trend. In this regard, the integration of photothermal therapy (PTT) with chemodynamic therapy (CDT), especially PTT/CDT in the second near-infrared (NIR-II) biowindow, has been demonstrated to be a highly efficient and relatively safe concept. With the rapid development of nanotechnology, nanoparticles can be designed from specific elements, such as Fe, that are equipped with both PTT and CDT therapeutic functions. In this review, we provide an update on the recent advances in Fe-based nanoplatforms for combined PTT/CDT. The perspectives on further improvement of the curative efficiency are described, highlighting the important scientific obstacles that require resolution in order to reach greater heights of clinical success. We hope this review will inspire the interest of researchers in developing novel Fe-based nanomedicines for multifunctional theranostics
Stem Cell Markers in Neuroblastoma—An Emerging Role for LGR5
No full textThe prognostic value of cancer stem cell markers in various cancer subtypes is a well documented research area. Our findings show that the stem cell marker Lgr5 is associated with an aggressive phenotype in neuroblastoma. Here, we discuss these findings within the context of recent studies in several cancers such as lung, colorectal and intestinal cancer, glioblastoma and ewing's sarcoma. Neuroblastoma continues to be an elusive disease, due to its heterogeneous presentation ranging from spontaneous regression to aggressive metastatic disease and intertwined genetic variability. Currently, the most significant prognostic marker of high risk disease and poor prognosis is amplification of the MYCN oncogene, which is found in approximately 25% of cases. With this in mind, there is still much to learn about the driving mechanisms of this aggressive pediatric tumor. Neuroblastoma development is thought to be the result of aberrant differentiation of the cell of origin, embryonic neural crest cells which then migrate and invade during the developmental stage. Aberrant cells are those which would, under normal conditions form the mature tissues of the sympathetic ganglia and adrenal medulla. Tumors are known to develop indiscriminately along the radius of the sympathetic ganglia, although it is well established that the adrenal glands are fundamentally the most common primary site
Abstract A22: Differentiation of human embryonic stem cells to sympathetic neurons: A potential model for understanding neuroblastoma pathogenesis
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