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.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.