Tumour stromal morphology impacts nanomedicine cytotoxicity in patient-derived xenografts

Understanding how tumour pathophysiology influences nanomedicine activity is challenging. We developed an advanced image analysis method to characterise the spatial distribution of apoptotic cells in 28 explant tumours, derived from one donor tumour, following treatment with liposomal doxorubicin. The analysis utilises standard immunohistochemistry images and quantifies the frequency of positive staining as a function of distance from the stroma. We classified two stromal morphologies: Tumour Island and Estuary, which differ in the convolution of the tumour-stroma boundary and proximity of tumour cells to vessels. Results reveal an 8.8-fold greater sensitivity to liposomal doxorubicin in the Estuary versus Tumour Island morphology.117