Title | Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | 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 |
Journal | Nature Biomedical Engineering |
Volume | 6 |
Issue | 10 |
Pagination | 1148 - 1166 |
Date Published | 10/19/2022 |
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. |
URL | https://www.nature.com/articles/s41551-022-00949-4 |
DOI | 10.1038/s41551-022-00949-4 |
Short Title | Nat. Biomed. Eng |