Brachytherapy via a depot of biopolymer-bound <sup>131</sup>I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.
Jeffrey L SchaalJayanta BhattacharyyaJeremy BrownsteinKyle C StricklandGarrett KellySoumen SahaJoshua J MilliganSamagya BanskotaXinghai LiWenge LiuDavid G KirschMichael R ZalutskyAshutosh ChilkotiPublished in: Nature biomedical engineering (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 (<sup>131</sup>I-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. <sup>131</sup>I-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 <sup>131</sup>I-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 <sup>131</sup>I-ELP depots for the synergistic treatment of localized pancreatic cancer.
Keyphrases
- locally advanced
- combination therapy
- rectal cancer
- radiation therapy
- neoadjuvant chemotherapy
- high dose
- squamous cell carcinoma
- phase ii study
- mouse model
- poor prognosis
- stem cells
- chemotherapy induced
- low dose
- iron oxide
- magnetic resonance imaging
- computed tomography
- single cell
- diabetic rats
- clinical trial
- mesenchymal stem cells
- radiation induced
- binding protein
- tissue engineering
- hyaluronic acid
- newly diagnosed
- stress induced