Cancer Patient Tissueoid with Self-Homing Nano-Targeting of Metabolic Inhibitor.

Abstract

The current paradigm of cancer medicine focuses on patient‐ and/or cancer‐specific treatments, which has led to continuous progress in the development of patient representatives (e.g., organoids) and cancer‐targeting carriers for drug screening. As breakthrough concepts, i) living cancer tissues convey intact profiles of patient‐specific microenvironmental signatures. ii) The growth mechanisms of cancer mass with intense cell‐cell interactions can be harnessed to develop self‐homing nano‐targeting by using cancer cell‐derived nanovesicles (CaNVs). Hence, a tissueoid model of ovarian cancer (OC) is developed by culturing OC patient tissues in a 3D gel chip, whose microchannel networks enable perfusion to maintain tissue viability. A novel model of systemic cancer responses is approached by xenografting OC tissueoids into ischaemic hindlimbs in nude mice. CaNVs are produced to carry general chemotherapeutics or new drugs under pre/clinical studies that target the BRCA mutation or energy metabolism, thereby increasing the test scope. This pioneer study cross‐validates drug responses from the OC clinic, tissueoid, and animal model by demonstrating the alignment of results in drug type‐specific efficiency, BRCA mutation‐dependent drug efficiency, and metabolism inhibition‐based anti‐cancer effects. Hence, this study provides a directional foundation to accelerate the discovery of patient‐specific drugs with CaNV application towards future precision medicine.