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

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Bhattacharyya, Jayanta

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Brownstein, Jeremy

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Strickland, Kyle C

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Kelly, Garrett

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Saha, Soumen

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Milligan, Joshua

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Banskota, Samagya

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Li, Xinghai

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Liu, Wenge

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Kirsch, David G

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Zalutsky, Michael R

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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

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2157-846X

dc.identifier.uri

https://hdl.handle.net/10161/26126

dc.language

eng

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Springer Science and Business Media LLC

dc.relation.ispartof

Nature biomedical engineering

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10.1038/s41551-022-00949-4

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Animals

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Mice

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Pancreatic Neoplasms

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Iodine Radioisotopes

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Paclitaxel

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Biopolymers

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Elastin

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Peptides

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Brachytherapy

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Nanoparticles

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Tumor Microenvironment

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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

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Pratt School of Engineering

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School of Medicine

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Trinity College of Arts & Sciences

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Clinical Science Departments

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Institutes and Centers

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Biomedical Engineering

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Pathology

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Radiation Oncology

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Radiology

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Duke Cancer Institute

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Chemistry

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Global Health Institute

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Initiatives

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Duke Innovation & Entrepreneurship

pubs.publication-status

Published

pubs.volume

6

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