| Literature DB >> 36261625 |
Jeffrey L Schaal1, Jayanta Bhattacharyya1,2, Jeremy Brownstein3, Kyle C Strickland4, Garrett Kelly1, Soumen Saha1, Joshua Milligan1, Samagya Banskota1, Xinghai Li1, Wenge Liu1, David G Kirsch3,5, Michael R Zalutsky1,3, Ashutosh Chilkoti6.
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.Entities:
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Year: 2022 PMID： 36261625 DOI： 10.1038/s41551-022-00949-4
Source DB: PubMed Journal: Nat Biomed Eng ISSN： 2157-846X Impact factor: 29.234