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

Publication ,  Journal Article
Schaal, JL; Bhattacharyya, J; Brownstein, J; Strickland, KC; Kelly, G; Saha, S; Milligan, J; Banskota, S; Li, X; Liu, W; Kirsch, DG ...
Published in: Nat Biomed Eng
October 2022

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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Published In

Nat Biomed Eng

DOI

EISSN

2157-846X

Publication Date

October 2022

Volume

6

Issue

10

Start / End Page

1148 / 1166

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • Peptides
  • Pancreatic Neoplasms
  • Paclitaxel
  • Nanoparticles
  • Mice
  • Iodine Radioisotopes
  • Elastin
  • Brachytherapy
  • Biopolymers
 

Citation

APA
Chicago
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Schaal, J. L., Bhattacharyya, J., Brownstein, J., Strickland, K. C., Kelly, G., Saha, S., … Chilkoti, A. (2022). Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours. Nat Biomed Eng, 6(10), 1148–1166. https://doi.org/10.1038/s41551-022-00949-4
Schaal, Jeffrey L., Jayanta Bhattacharyya, Jeremy Brownstein, Kyle C. Strickland, Garrett Kelly, Soumen Saha, Joshua Milligan, et al. “Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.Nat Biomed Eng 6, no. 10 (October 2022): 1148–66. https://doi.org/10.1038/s41551-022-00949-4.
Schaal JL, Bhattacharyya J, Brownstein J, Strickland KC, Kelly G, Saha S, et al. Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours. Nat Biomed Eng. 2022 Oct;6(10):1148–66.
Schaal, Jeffrey L., et al. “Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.Nat Biomed Eng, vol. 6, no. 10, Oct. 2022, pp. 1148–66. Pubmed, doi:10.1038/s41551-022-00949-4.
Schaal JL, Bhattacharyya J, Brownstein J, Strickland KC, Kelly G, Saha S, Milligan J, Banskota S, Li X, Liu W, Kirsch DG, Zalutsky MR, Chilkoti A. Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours. Nat Biomed Eng. 2022 Oct;6(10):1148–1166.

Published In

Nat Biomed Eng

DOI

EISSN

2157-846X

Publication Date

October 2022

Volume

6

Issue

10

Start / End Page

1148 / 1166

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • Peptides
  • Pancreatic Neoplasms
  • Paclitaxel
  • Nanoparticles
  • Mice
  • Iodine Radioisotopes
  • Elastin
  • Brachytherapy
  • Biopolymers