Tumour stromal morphology impacts nanomedicine cytotoxicity in patient-derived xenografts

Nanomedicine : Nanotechnology, Biology, and Medicine
Juan A Delgado San MartinSimon T Barry

Abstract

It is challenging to evaluate how tumour pathophysiology influences nanomedicine therapeutic effect; however, this is a key question in drug delivery. An advanced analytical method was developed to quantify the spatial distribution of drug-induced effect in tumours with varied stromal morphologies. The analysis utilises standard immunohistochemistry images and quantifies the frequency of positive staining as a function of distance from the stroma. Two stromal morphologies - Estuary and Tumour Island - were classified in 28 tumours from a lung cancer explant model in mice treated with liposomal doxorubicin. Analysis demonstrated that Estuary-like tumours presented a highly convoluted tumour-stroma interface, with most tumour cells in close proximity to vessels; these tumours were 8.8-fold more responsive to liposomal doxorubicin than were Tumour Island-like tumours, which were nearly unresponsive to liposomal doxorubicin. SDARS analysis allows the relative treatment effect to be assessed in tumours individually, and enables investigation of nanomedicine delivery in complex tumour pathophysiologies. Advances in nanotechnology have brought about many novel treatment modalities for cancer. Nonetheless, there is no standard evaluati...Continue Reading

References

Mar 4, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·H MaedaK Hori
Sep 29, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Twan LammersGert Storm
Sep 14, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Neil R SmithSimon T Barry

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Citations

May 4, 2016·Advanced Drug Delivery Reviews·Jennifer I HareSimon T Barry
Oct 31, 2015·PLoS Computational Biology·Juan A Delgado-SanMartinJames W T Yates
Jun 23, 2020·Clinical Pharmacology and Therapeutics·James W T YatesPaolo Vicini
Jun 1, 2017·BMC Medical Informatics and Decision Making·J A Delgado-SanMartinJ W T Yates

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