A 3D Cell Culture Platform for Evaluating Macrophage‐Liposome Conjugates in Combination Chemotherapy

• Published in: Journal of biomedical materials research. Part A Vol. 113; no. 6; pp. e37939 - n/a
• Main Authors: Kuo, Chia‐Chen, Liao, Wei‐Yu, Lin, Yu‐Jung, Lee, Chau‐Hwang
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2025; Wiley Subscription Services, Inc
• Subjects: 3D cell culture; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Cell culture; Cell Culture Techniques, Three Dimensional - methods; Cell Line, Tumor; Cell migration; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cisplatin - pharmacology; combination chemotherapy; Conjugates; Design optimization; Dosage; Drug delivery; Drug Delivery Systems; Drug dosages; Homing behavior; Humans; liposome; Liposomes; Liposomes - chemistry; macrophage; Macrophages; Macrophages - cytology; Macrophages - metabolism; Mice; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - pharmacology; Solid tumors; Tumors; 3D cell culture; macrophage; liposome; combination chemotherapy
• ISSN: 1549-3296; 1552-4965; 1552-4965
• DOI: 10.1002/jbm.a.37939

ABSTRACT 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.