Brachytherapy via a depot of biopolymer-bound <sup>131</sup>I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.

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.

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Citation

Published Version (Please cite this version)

10.1038/s41551-022-00949-4

Publication Info

Schaal, Jeffrey L, Jayanta Bhattacharyya, Jeremy Brownstein, Kyle C Strickland, Garrett Kelly, Soumen Saha, Joshua Milligan, Samagya Banskota, et al. (2022). Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours. Nature biomedical engineering, 6(10). pp. 1148–1166. 10.1038/s41551-022-00949-4 Retrieved from https://hdl.handle.net/10161/26126.

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Scholars@Duke

Strickland

Kyle C. Strickland

Adjunct Associate Professor of Pathology

Dr. Strickland specializes in cytopathology and women's and perinatal surgical pathology.  His areas of interest include epithelial and mesenchymal gynecologic neoplasia and fine needle aspiration cytology.

Soumen Saha

Research Scientist, Senior
Kirsch

David Guy Kirsch

Adjunct Professor in the Department of Radiation Oncology

My clinical interests are the multi-modality care of patients with bone and soft tissue sarcomas and developing new sarcoma therapies. My laboratory interests include utilizing mouse models of cancer to study cancer and radiation biology in order to develop new cancer therapies in the pre-clinical setting.


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