ORCID Profile
0000-0002-7986-8173
Current Organisation
University of Melbourne
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Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7NR07814E
Abstract: A dynamic DNA nanoswitch is used to probe NF-κB binding activity and its expression level directly in living cells.
Publisher: American Chemical Society (ACS)
Date: 19-12-2019
Abstract: The intracellular delivery of nucleic acids and proteins remains a key challenge in the development of biological therapeutics. In gene therapy, the inefficient delivery of small interfering RNA (siRNA) to the cytosol by lipoplexes or polyplexes is often ascribed to the entrapment and degradation of siRNA payload in the endosomal compartments. A possible mechanism by which polyplexes rupture the endosomal membrane and release their nucleic acid cargo is commonly defined as the "proton sponge effect". This is an osmosis-driven process triggered by the proton buffering capacity of polyplexes. Herein, we investigate the molecular basis of the "proton sponge effect" through direct visualization of the siRNA trafficking process, including analysis of in idual polyplexes and endosomes, using stochastic optical reconstruction microscopy. We probe the sequential siRNA trafficking steps through single molecule super-resolution analysis of subcellular structures, polyplexes, and silencing RNA molecules. Specifically, in idual intact polyplexes released in the cytosol upon rupture of the endosomes, the damaged endosomal vesicles, and the disassembly of the polyplexes in the cytosol are examined. We find that the architecture of the polyplex and the rigidity of the cationic polymer chains are crucial parameters that control the mechanism of endosomal escape driven by the proton sponge effect. We provide evidence that in highly branched and rigid cationic polymers, such as glycogen or polyethylenimine, immobilized on silica nanoparticles, the proton sponge effect is effective in inducing osmotic swelling and rupture of endosomes.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0NR03087B
Abstract: The intracellular interactions and fate of a DNA nanosensor were investigated by combining quantitative microscopy and stochastic optical reconstruction microscopy.
Publisher: Wiley
Date: 06-08-2020
Publisher: Wiley
Date: 30-01-2022
Abstract: The integration of bioactive materials (e.g., proteins and genes) into nanoparticles holds promise in fields ranging from catalysis to biomedicine. However, it is challenging to develop a simple and broadly applicable nanoparticle platform that can readily incorporate distinct biomacromolecules without affecting their intrinsic activity. Herein, a metal–phenolic assembly approach is presented whereby erse functional nanoparticles can be readily assembled in water by combining various synthetic and natural building blocks, including poly(ethylene glycol), phenolic ligands, metal ions, and bioactive macromolecules. The assembly process is primarily mediated by metal–phenolic complexes through coordination and hydrophobic interactions, which yields uniform and spherical nanoparticles (mostly nm), while preserving the function of the incorporated biomacromolecules (siRNA and five different proteins used). The functionality of the assembled nanoparticles is demonstrated through cancer cell apoptosis, RNA degradation, catalysis, and gene downregulation studies. Furthermore, the resulting nanoparticles can be used as building blocks for the secondary engineering of superstructures via templating and cross‐linking with metal ions. The bioactivity and versatility of the platform can potentially be used for the streamlined and rational design of future bioactive materials.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0TB00299B
Abstract: Amphiphilic phytoglycogen nanoparticles are used as building blocks for engineering multifunctional hybrid films with catalytic and sensing properties.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.BIOMATERIALS.2018.05.024
Abstract: The poor penetration of nanocarrier-siRNA constructs into tumor tissue is a major hurdle for the in vivo efficacy of siRNA therapeutics, where the ability of the constructs to permeate the 3D multicellular matrix is determined by their physicochemical properties. Herein, we optimized the use of soft glycogen nanoparticles for the engineering of glycogen-siRNA constructs that can efficiently penetrate multicellular tumor spheroids and exert a significant gene silencing effect. Glycogen nanoparticles from different bio-sources and with different structural features were investigated. We show that larger glycogen nanoparticles ranging from 50 to 80 nm are suboptimal systems for complexation of nucleic acids if fine control of the size of constructs is required. Our studies suggest that 20 nm glycogen nanoparticles are optimal for complexation and efficient delivery of siRNA. The chemical composition, surface charge, and size of glycogen-siRNA constructs were finely controlled to minimize interactions with serum proteins and allow penetration into 3D multicellular spheroids of human kidney epithelial cells and human prostate cancer cells. We introduced pH sensitive moieties within the construct to enhance early endosome escape and efficiently improve the silencing effect in vitro. Glycogen-siRNA constructs were found to mediate gene silencing in 3D multicellular spheroids causing ∼60% specific gene silencing. The optimized construct exhibited an in vivo circulation lifetime of 8 h in mice, with preferential accumulation in the liver. No accumulation in the kidney, lung, spleen, heart or brain, or signs of toxicity in mice were observed. Our results highlight the potential for screening siRNA nanocarriers in 3D cultured prostate tumor models, thereby improving the predictive therapeutic efficacy of glycogen-based platforms in human physiological conditions.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1NR08429A
Abstract: Nanocomplexes of glycogen nanoparticles with serum albumin were formed by triggering the nanophase separation of albumin. The nanocomplexes enabled the delivery of chemotherapeutics in complex multicellular 3D tumour-like structures.
Publisher: American Chemical Society (ACS)
Date: 10-2019
Abstract: The intracellular delivery of functional nanoparticles (NPs) and the release of therapeutic payloads at a target site are central issues for biomedical applications. However, the endosomal entrapment of NPs typically results in the degradation of active cargo, leading to poor therapeutic outcomes. Current advances to promote the endosomal escape of NPs largely involve the use of polycationic polymers and cell-penetrating peptides (CPPs), which both can suffer from potential toxicity and convoluted synthesis/conjugation processes. Herein, we report the use of metal-phenolic networks (MPNs) as versatile and nontoxic coatings to facilitate the escape of NPs from endo/lysosomal compartments. The MPNs, which were engineered from the polyphenol tannic acid and Fe
Publisher: American Chemical Society (ACS)
Date: 29-07-2020
No related grants have been discovered for Agata Radziwon.