A <scp>3D</scp> Cell Culture Platform for Evaluating Macrophage‐Liposome Conjugates in Combination Chemotherapy

Macrophage-based drug delivery systems, such as macrophage-liposome conjugates (Mϕ-Lip), leverage the natural tumor-homing ability of macrophages and offer a potential solution for overcoming biological barriers and delivering chemotherapy drugs to challenging tumor regions. However, reliable platforms to assess the tumor-targeting efficiency, penetration capabilities, and therapeutic effectiveness of drug-laden macrophages remain largely unavailable. In this study, we developed a three-dimensional (3D) cell culture platform that mimics the structural and biological complexity of in vivo tumors, enabling real-time observation and analysis of Mϕ-Lip as they migrate, penetrate, and exert anti-tumor effects. Beyond evaluating the delivery process, this work focuses on the rational design and optimization of dosage regimens for co-delivering cisplatin (CDDP) and paclitaxel (Taxol) using Mϕ-Lip. Experimental results demonstrated that the drugs encapsulated within the liposomes influenced the invasive behavior of Mϕ-Lip, which in turn impacted their tumor-killing efficiency. Using this 3D cell culture platform, we identified optimal dosage regimens for co-delivering combination chemotherapy drugs through the Mϕ-Lip. This newly developed approach provides a reliable and versatile tool not only for evaluating but also for fine-tuning cell-based drug delivery strategies. It holds significant promise for advancing targeted chemotherapy strategies and improving therapeutic outcomes for solid tumors.