Evaluation of the activity of a chemo-ablative, thermoresponsive hydrogel in a murine xenograft model of lung cancer
Background: Minimally invasive intratumoural administration of thermoresponsive hydrogels, that transition from liquid to gel in response to temperature, has been proposed as a potential treatment modality for solid tumours. The aim of this study was to assess the inherent cytotoxicity of a poloxamer-based thermoresponsive hydrogel in a murine xenograft model of lung cancer.
Methods: In vitro viability assessment was carried out in a lung cancer (A549) and non-cancerous (Balb/c 3T3 clone A31) cell line. Following intratumoural administration of saline or the thermoresponsive hydrogel to an A549 xenograft model in female Athymic Nude-Foxn1nu mice (n = 6/group), localisation was confirmed using IVIS imaging. Tumour volume was assessed using callipers measurements over 14 days. Blood serum was analysed for liver and kidney damage and ex vivo tissue samples were histologically assessed.
Results: The thermoresponsive hydrogel demonstrated a dose-dependent cancer cell-specific toxicity in vitro and was retained in situ for at least 14 days in the xenograft model. Tumour volume increase was statistically significantly lower than saline treated control at day 14 (n = 6, p = 0.0001), with no associated damage of hepatic or renal tissue observed.
Conclusions: Presented is a poloxamer-based thermoresponsive hydrogel, suitable for intratumoural administration and retention, which has demonstrated preliminary evidence of local tumour control, with minimal off-site toxicity.
Enterprise Ireland Commercialisation Fund (CF-2016-0431P)
RCSI School of Pharmacy bursary
CommentsThe original article is available at https://www.nature.com
Published CitationRossi SM, Ryan BK, Kelly HM. Evaluation of the activity of a chemo-ablative, thermoresponsive hydrogel in a murine xenograft model of lung cancer. Br J Cancer. 2020;123(3):369-377.
Publication Date27 May 2020
- Anatomy and Regenerative Medicine
- RCSI Tissue Engineering Group (TERG)
- School of Pharmacy and Biomolecular Sciences
- Biomaterials and Regenerative Medicine
- Chemistry and Pharmaceutical Sciences
- Neurological and Psychiatric Disorders
- Population Health and Health Services
PublisherNature Publishing Group on behalf of Cancer Research UK
- Published Version (Version of Record)