The performance and environmental impact of pro-oxidant additive containing plastics in the open unmanaged environment—a review of the evidence

Pro-oxidant additive containing (PAC) plastics is a term that describes a growing number of plastics which are designed to degrade in the unmanaged natural environment (open-air, soil, aquatic) through oxidation and other processes. It is a category that includes ‘oxo-degradable’ plastics, ‘oxo-biodegradable’ plastics and those containing ‘biotransformation’ additives. There is evidence that a new standard PAS 9017 : 2020 is relevant to predicting the timescale for abiotic degradation of PAC plastic in hot dry climates under ideal conditions (data reviewed for South of France and Florida). There are no reliable data to date to show that the PAS 9017 : 2020 predicts the timescale for abiotic degradation of PAC plastics in cool or wet climatic regions such as the UK or under less ideal conditions (soil burial, surface soiling etc.). Most PAC plastics studied in the literature showed biodegradability values in the range 5–60% and would not pass the criteria for biodegradability set in the new PAS 9017 : 2020. Possible formation of microplastics and cross-linking have been highlighted both by field studies and laboratory studies. Systematic eco-toxicity studies are needed to assess the possible effect of PAC additives and microplastics on the environment and biological organisms

EGFR-targeted semiconducting polymer nanoparticles for photoacoustic imaging

Semiconducting polymer nanoparticles (SPN), formulated from organic semiconducting polymers and lipids, show promise as exogenous contrast agents for photoacoustic imaging (PAI). To fully realise the potential of this class of nanoparticles for imaging and therapeutic applications, a broad range of active targeting strategies, where ligands specific to receptors on the target cells are displayed on the SPN surface, are urgently needed. In addition, effective strategies for quantifying the level of surface modification are also needed to support development of ligand-targeted SPN. In this paper, we have developed methods to prepare SPN bearing peptides targeted to Epidermal Growth Factor Receptors (EGFR), which are overexpressed at the surface of a wide variety of cancer cell types. In addition to fully characterising these targeted nanoparticles by standard methods (UV–visible, photoacoustic absorption, dynamic light scattering, zeta potential and SEM), we have developed a powerful new NMR method to determine the degree of conjugation and the number of targeting peptides attached to the SPN. Preliminary in vitro experiments with the colorectal cancer cell line LIM1215 indicated that the EGFR-targeting peptide conjugated SPN were either ineffective in delivering the SPN to the cells, or that the targeting peptide itself destabilised the formulation. This in reinforces the need for effective characterisation techniques to measure the surface accessibility of targeting ligands attached to nanoparticles

EGFR-targeted semiconducting polymer nanoparticles for photoacoustic imaging

Semiconducting polymer nanoparticles (SPN), formulated from organic semiconducting polymers and lipids, show promise as exogenous contrast agents for photoacoustic imaging (PAI). To fully realise the potential of this class of nanoparticles for imaging and therapeutic applications, a broad range of active targeting strategies, where ligands specific to receptors on the target cells are displayed on the SPN surface, are urgently needed. In addition, effective strategies for quantifying the level of surface modification are also needed to support development of ligand-targeted SPN. In this paper, we have developed methods to prepare SPN bearing peptides targeted to Epidermal Growth Factor Receptors (EGFR), which are overexpressed at the surface of a wide variety of cancer cell types. In addition to fully characterising these targeted nanoparticles by standard methods (UV-visible, photoacoustic absorption, dynamic light scattering, zeta potential and SEM), we have developed a powerful new NMR method to determine the degree of conjugation and the number of targeting peptides attached to the SPN. Preliminary in vitro experiments with the colorectal cancer cell line LIM1215 indicated that the EGFR-targeting peptide conjugated SPN were either ineffective in delivering the SPN to the cells, or that the targeting peptide itself destabilised the formulation. This in reinforces the need for effective characterisation techniques to measure the surface accessibility of targeting ligands attached to nanoparticles

Investigating the performance of a novel pH and cathepsin B sensitive, stimulus-responsive nanoparticle for optimised sonodynamic therapy in prostate cancer

Nano-formulations that are responsive to tumour-related and externally-applied stimuli can offer improved, site-specific antitumor effects, and can improve the efficacy of conventional therapeutic agents. Here, we describe the performance of a novel stimulus-responsive nanoparticulate platform for the targeted treatment of prostate cancer using sonodynamic therapy (SDT). The nanoparticles were prepared by self-assembly of poly(L-glutamic acid-L-tyrosine) co-polymer with hematoporphyrin. The nanoparticulate formulation was characterized with respect to particle size, morphology, surface charge and singlet oxygen production during ultrasound exposure. The response of the formulation to the presence of cathepsin B, a proteolytic enzyme that is overexpressed and secreted in the tumour microenvironment of many solid tumours, was assessed. Our results showed that digestion with cathepsin B led to nanoparticle size reduction. In the absence of ultrasound, the formulation exhibited greater toxicity at acidic pH than at physiological pH, using the human prostate cells lines LNCaP and PC3 as targets. Nanoparticle cellular uptake was enhanced at acidic pH – a condition that was also associated with greater cathepsin B production. Nanoparticles exhibited enhanced ultrasound-induced cytotoxicity against both prostate cancer cell lines. Subsequent proof-of-concept in vivo studies demonstrated that, when ectopic human xenograft LNCaP tumours in SCID mice were treated with SDT using the systemically-administered nanoparticulate formulation at a single dose, tumour volumes decreased by up to 64% within 24 h. No adverse effects were observed in the nanoparticle-treated mice and their body weight remained stable. The potential of this novel formulation to deliver safe and effective treatment of prostate cancer is discussed

Nanotechnology-augmented sonodynamic therapy and associated immune-mediated effects for the treatment of pancreatic ductal adenocarcinoma

PURPOSE: Sonodynamic therapy (SDT) is emerging as a cancer treatment alternative with significant advantages over conventional therapies, including its minimally invasive and site-specific nature, its radical antitumour efficacy with minimal side effects, and its capacity to raise an antitumour immune response. The study explores the efficacy of SDT in combination with nanotechnology against pancreatic ductal adenocarcinoma. METHODS: A nanoparticulate formulation (HPNP) based on a cathepsin B-degradable glutamate-tyrosine co-polymer that carries hematoporphyrin was used in this study for the SDT-based treatment of PDAC. Cathepsin B levels in BxPC-3 and PANC-1 cells were correlated to cellular uptake of HPNP. The HPNP efficiency to induce a sonodynamic effect at varying ultrasound parameters, and at different oxygenation and pH conditions, was investigated. The biodistribution, tumour accumulation profile, and antitumour efficacy of HPNP in SDT were examined in immunocompetent mice carrying bilateral ectopic murine pancreatic tumours. The immune response profile of excised tumour tissues was also examined. RESULTS: The HPNP formulation significantly improved cellular uptake of hematoporphyrin for both BxPC-3 and PANC-1 cells, while increase of cellular uptake was positively correlated in PANC-1 cells. There was a clear SDT-induced cytotoxicity at the ultrasound conditions tested, and the treatment impaired the capacity of both BxPC-3 and PANC-1 cells to form colonies. The overall acoustic energy and pulse length, rather than the power density, were key in eliciting the effects observed in vitro. The SDT treatment in combination with HPNP resulted in 21% and 27% reduction of the target and off-target tumour volumes, respectively, within 24 h. A single SDT treatment elicited an antitumour effect that was characterized by an SDT-induced decrease in immunosuppressive T cell phenotypes. CONCLUSION: SDT has significant potential to serve as a monotherapy or adjunctive treatment for inoperable or borderline resectable PDAC

Binding of a Protein or a Small Polyelectrolyte onto Synthetic Vesicles

Catanionic vesicles were prepared by mixing nonstoichiometric amounts of sodium bis(2-ethylhexyl) sulfosuccinate and dioctyldimethylammonium bromide in water. Depending on the concentration and mole ratios between the surfactants, catanionic vesicular aggregates are formed. They have either negative or positive charges in excess and are endowed with significant thermodynamic and kinetic stability. Vesicle characterization was performed by dynamic light scattering and electrophoretic mobility. It was inferred that vesicle size scales in inverse proportion with its surface charge density and diverges as the latter quantity approaches zero and/or the mole ratio equals unity. Therefore, both variables are controlled by the anionic/cationic mole ratio. Small-angle X-ray scattering, in addition, indicates that vesicles are unilamellar. Selected anionic vesicular systems were reacted with poly-L-lysine hydrobromide or lysozyme. Polymer binding continues until complete neutralization of the negatively charged sites on the vesicles surface is attained, as inferred by electrophoretic mobility. Lipoplexes are formed as a result of significant electrostatic interactions between cationic polyelectrolytes and negatively charged vesicles

The performance and environmental impact of pro-oxidant additive containing plastics in the open unmanaged environment—a review of the evidence

Pro-oxidant additive containing (PAC) plastics is a term that describes a growing number of plastics which are designed to degrade in the unmanaged natural environment (open-air, soil, aquatic) through oxidation and other processes. It is a category that includes ‘oxo-degradable’ plastics, ‘oxo-biodegradable’ plastics and those containing ‘biotransformation’ additives. There is evidence that a new standard PAS 9017 : 2020 is relevant to predicting the timescale for abiotic degradation of PAC plastic in hot dry climates under ideal conditions (data reviewed for South of France and Florida). There are no reliable data to date to show that the PAS 9017 : 2020 predicts the timescale for abiotic degradation of PAC plastics in cool or wet climatic regions such as the UK or under less ideal conditions (soil burial, surface soiling etc.). Most PAC plastics studied in the literature showed biodegradability values in the range 5–60% and would not pass the criteria for biodegradability set in the new PAS 9017 : 2020. Possible formation of microplastics and cross-linking have been highlighted both by field studies and laboratory studies. Systematic eco-toxicity studies are needed to assess the possible effect of PAC additives and microplastics on the environment and biological organisms

Ion distribution around synthetic vesicles of the cat-anionic type.

Aqueous alkyltrimethylammonium bromides, or dialkyldimethylammonium ones, were mixed with sodium alkyl sulfates and dialkanesulfonates. Depending on the overall surfactant concentration, charge and/or mole ratios, cat-anionic vesicles were formed by mixing nonstoichiometric amounts of oppositely charged species. The resulting vesicles are thermodynamically and kinetically stable. zeta-potential and dynamic light scattering characterized the systems. As a rule, cat-anionic vesicles have sizes in the 10(2)-10(3) nm range and bear significant amounts of surface charges. At fixed surfactant concentration, the vesicle surface charge density scales with mole ratios and tends to zero as the latter approach unity. Conversely, the hydrodynamic radius diverges when the cationic/anionic mole ratio is close to 1. The double-layer thickness and surface charge density are controlled by mole ratios and addition of NaBr, which plays a role in vesicle stability. The salt screens the surface charge density and modulates both vesicle size and double-layer thickness. Slightly higher concentrations of NaBr induce the transition from vesicles toward lamellar phases. The electrokinetic properties of cat-anionic dispersions were analyzed by dielectric relaxation experiments. The measured properties are sensitive to vesicle size distributions. In fact, the relaxation frequency shifts in proportion to vesicle polydispersity. Model calculations proposed on that purpose supported the experimental findings