Publications [#367376] of Ashutosh Chilkoti

Papers Published

1. 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, vol. 6 no. 10 (October, 2022), pp. 1148-1166 [doi]
   (last updated on 2026/01/14)

   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.