Brachytherapy via a depot of biopolymer-bound <sup>131</sup>I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.
dc.contributor.author | Schaal, Jeffrey L | |
dc.contributor.author | Bhattacharyya, Jayanta | |
dc.contributor.author | Brownstein, Jeremy | |
dc.contributor.author | Strickland, Kyle C | |
dc.contributor.author | Kelly, Garrett | |
dc.contributor.author | Saha, Soumen | |
dc.contributor.author | Milligan, Joshua | |
dc.contributor.author | Banskota, Samagya | |
dc.contributor.author | Li, Xinghai | |
dc.contributor.author | Liu, Wenge | |
dc.contributor.author | Kirsch, David G | |
dc.contributor.author | Zalutsky, Michael R | |
dc.contributor.author | Chilkoti, Ashutosh | |
dc.date.accessioned | 2022-11-01T13:27:39Z | |
dc.date.available | 2022-11-01T13:27:39Z | |
dc.date.issued | 2022-10 | |
dc.date.updated | 2022-11-01T13:27:24Z | |
dc.description.abstract | 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 (131I-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. 131I-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 131I-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 131I-ELP depots for the synergistic treatment of localized pancreatic cancer. | |
dc.identifier | 10.1038/s41551-022-00949-4 | |
dc.identifier.issn | 2157-846X | |
dc.identifier.issn | 2157-846X | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.relation.ispartof | Nature biomedical engineering | |
dc.relation.isversionof | 10.1038/s41551-022-00949-4 | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Pancreatic Neoplasms | |
dc.subject | Iodine Radioisotopes | |
dc.subject | Paclitaxel | |
dc.subject | Biopolymers | |
dc.subject | Elastin | |
dc.subject | Peptides | |
dc.subject | Brachytherapy | |
dc.subject | Nanoparticles | |
dc.subject | Tumor Microenvironment | |
dc.subject | Albumin-Bound Paclitaxel | |
dc.title | Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours. | |
dc.type | Journal article | |
duke.contributor.orcid | Strickland, Kyle C|0000-0003-1636-5277 | |
duke.contributor.orcid | Saha, Soumen|0000-0003-3533-6703 | |
duke.contributor.orcid | Zalutsky, Michael R|0000-0002-5456-0324 | |
pubs.begin-page | 1148 | |
pubs.end-page | 1166 | |
pubs.issue | 10 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Pratt School of Engineering | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Trinity College of Arts & Sciences | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Biomedical Engineering | |
pubs.organisational-group | Pathology | |
pubs.organisational-group | Radiation Oncology | |
pubs.organisational-group | Radiology | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Chemistry | |
pubs.organisational-group | Institutes and Provost's Academic Units | |
pubs.organisational-group | University Institutes and Centers | |
pubs.organisational-group | Duke Global Health Institute | |
pubs.organisational-group | Initiatives | |
pubs.organisational-group | Duke Innovation & Entrepreneurship | |
pubs.publication-status | Published | |
pubs.volume | 6 |
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