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. doi: 10.1038/s41551-022-00949-4. Epub 2022 Oct 19.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Albumin-Bound Paclitaxel
  • Animals
  • Biopolymers
  • Brachytherapy*
  • Elastin
  • Iodine Radioisotopes / therapeutic use
  • Mice
  • Nanoparticles*
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / radiotherapy
  • Peptides
  • Tumor Microenvironment


  • Elastin
  • Iodine-131
  • Albumin-Bound Paclitaxel
  • Paclitaxel
  • Iodine Radioisotopes
  • Biopolymers
  • Peptides