Brachytherapy via a depot of biopolymer-bound 131 I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours
Nature Biomedical Engineering(2022)
摘要
Locally advanced pancreatic tumours are highly resistant to conventional radiochemotherapy. Here we show that such resistance can be surmounted by an injectable depot of thermally responsive elastin-like polypeptide (ELP) conjugated with iodine-131 radionuclides ( 131 I-ELP) when combined with systemically delivered nanoparticle albumin-bound paclitaxel. This combination therapy induced complete tumour regressions in diverse subcutaneous and orthotopic mouse models of locoregional pancreatic tumours. 131 I-ELP brachytherapy was effective independently of the paclitaxel formulation and dose, but external beam radiotherapy (EBRT) only achieved tumour-growth inhibition when co-administered with nanoparticle paclitaxel. Histological analyses revealed that 131 I-ELP brachytherapy led to changes in the expression of intercellular collagen and junctional proteins within the tumour microenvironment. These changes, which differed from those of EBRT-treated tumours, correlated with the improved delivery and accumulation of paclitaxel nanoparticles within the tumour. Our findings support the further translational development of 131 I-ELP depots for the synergistic treatment of localized pancreatic cancer.
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关键词
Cancer therapeutic resistance,Drug development,Pancreatic cancer,Radiotherapy,Biomedicine,general,Biomedical Engineering/Biotechnology
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