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

IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL
Chia-Chen Kuo, Wei-Yu Liao, Yu-Jung Lin, Chau-Hwang Lee
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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.

联合化疗中巨噬-脂质体结合物的三维细胞培养平台评价
巨噬细胞为基础的药物传递系统,如巨噬细胞-脂质体偶联物(m -lip),利用巨噬细胞的天然肿瘤定位能力,为克服生物屏障和将化疗药物输送到具有挑战性的肿瘤区域提供了一种潜在的解决方案。然而,目前尚无可靠的平台来评估载药巨噬细胞的肿瘤靶向效率、渗透能力和治疗效果。在这项研究中,我们开发了一种三维(3D)细胞培养平台,模拟体内肿瘤的结构和生物学复杂性,能够实时观察和分析m.d. - lip的迁移,穿透和发挥抗肿瘤作用。除了评估给药过程外,本研究还侧重于合理设计和优化使用m不言自明- lip联合给药顺铂(CDDP)和紫杉醇(Taxol)的给药方案。实验结果表明,包封在脂质体内的药物影响了miss - lip的侵袭行为,从而影响了它们的肿瘤杀伤效率。利用这种3D细胞培养平台,我们确定了通过m - lip共同递送联合化疗药物的最佳剂量方案。这种新开发的方法不仅为评估而且为微调基于细胞的药物递送策略提供了可靠和通用的工具。它对推进靶向化疗策略和改善实体瘤的治疗结果具有重要的前景。
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来源期刊
Journal of biomedical materials research. Part A
Journal of biomedical materials research. Part A 工程技术-材料科学:生物材料
CiteScore
10.40
自引率
2.00%
发文量
135
审稿时长
3.6 months
期刊介绍: The Journal of Biomedical Materials Research Part A is an international, interdisciplinary, English-language publication of original contributions concerning studies of the preparation, performance, and evaluation of biomaterials; the chemical, physical, toxicological, and mechanical behavior of materials in physiological environments; and the response of blood and tissues to biomaterials. The Journal publishes peer-reviewed articles on all relevant biomaterial topics including the science and technology of alloys,polymers, ceramics, and reprocessed animal and human tissues in surgery,dentistry, artificial organs, and other medical devices. The Journal also publishes articles in interdisciplinary areas such as tissue engineering and controlled release technology where biomaterials play a significant role in the performance of the medical device. The Journal of Biomedical Materials Research is the official journal of the Society for Biomaterials (USA), the Japanese Society for Biomaterials, the Australasian Society for Biomaterials, and the Korean Society for Biomaterials. Articles are welcomed from all scientists. Membership in the Society for Biomaterials is not a prerequisite for submission.
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