Description
Nanodiamond (ND) has been demonstrated with exceptional biocompatibility and low cytotoxicity across various cell lines, establishing it as a reliable and safe platform for use as a nanocarrier in biological and medical applications. In this study, ND-HSA-DOX was formed by conjugating human serum albumin (HSA) and doxorubicin (DOX) with ND. ND can deliver drugs to tumour microenvironments, while HSA prevents the composite from aggregating. In our previous work, we used human alveolar basal epithelial cells (A549) and human normal lung fibroblast cells (HFL1) to develop three types of 3D co-culture models: “single type of cancerous cell,” “mixed co-culture,” and “core-shell co-culture” multicellular tumour spheroids (MCTS). Compared to 2D models, 3D MCTS are closer to real human conditions and better mimic the microenvironment in vivo. The cytotoxic effects of ND, pure DOX, and the ND-HSA-DOX complex were assessed in three types of 3D MCTS models via a growth inhibition assay. Our results show that ND-HSA-DOX has better cancer-inhibiting efficacy compared to the pure drug DOX in 3D co-culture MCTS. The crucial gene MDR1 (Multi-drug resistance) is known for causing drug resistance, leading to the efflux of drugs by P-gp (P-glycoprotein). P-gp is an ATP-binding cassette (ABC) transporter on the cell membrane that acts as an efflux pump to regulate potentially harmful substances within the cell. In this work, we used pure DOX and ND-HSA-DOX in 2D models of A549 cells to verify the characteristics of P-gp and compare its interactions with different treatments.