Bang Jooin, Yeo Jiyoung, Lee Su Ji, Lee Hansol, Kim Jinyoung, Jeong Sohyeon, Kang Eeseul, Rho Hoon Suk, Kim YongTae, Park Jun-Ook
Department of Otolaryngology-Head and Neck Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Medical Life Sicences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Biomed Microdevices. 2025 Jun 2;27(2):25. doi: 10.1007/s10544-025-00748-z.
Conventional in vitro cancer models often fail to replicate the complexity of the tumor microenvironment. We have developed a 3D micro-engineered vascularized organoid chip (VOC) platform to enhance the physiological relevance of in vivo tumor models. This platform incorporates patient-derived tumor spheroids from head and neck cancer patients, providing a more accurate simulation of the native tumor microenvironment. We evaluated the efficacy of 5-fluorouracil (5-FU) and sunitinib on angiogenic sprouting and cell viability of red fluorescent protein-expressing human umbilical vein endothelial cells (RFP-HUVECs) and head and neck cancer patient-derived tumor spheroids cultured in the VOC platform. A 3D micro-engineered VOC platform was developed to provide a physiologically relevant environment for RFP-HUVECs and head and neck cancer patient-derived tumor spheroids. Cellular responses to 5-FU and sunitinib were examined over 14 days, focusing on interactions and behavior in the VOC setup. 5-FU and sunitinib significantly inhibited angiogenic sprouting and reduced cell viability. Notably, these drugs induced changes in cellular network formation and disrupted the structural integrity of patient-derived spheroids, emphasizing the effectiveness of these drugs in a model that closely simulates the tumor microenvironment of head and neck cancer. Our study demonstrates the potential of the 3D vascularized tumor spheroid microfluidic chip as a valuable tool for personalized treatment and investigation of head and neck squamous cell carcinoma. This platform simulates the tumor microenvironment and offers exceptional precision in evaluating drug efficacy.
传统的体外癌症模型往往无法复制肿瘤微环境的复杂性。我们开发了一种三维微工程化血管化类器官芯片（VOC）平台，以增强体内肿瘤模型的生理相关性。该平台整合了头颈癌患者来源的肿瘤球，能更准确地模拟天然肿瘤微环境。我们评估了5-氟尿嘧啶（5-FU）和舒尼替尼对在VOC平台中培养的红色荧光蛋白表达人脐静脉内皮细胞（RFP-HUVECs）和头颈癌患者来源的肿瘤球血管生成芽生和细胞活力的影响。开发了一种三维微工程化VOC平台，为RFP-HUVECs和头颈癌患者来源的肿瘤球提供生理相关环境。在14天内检测细胞对5-FU和舒尼替尼的反应，重点关注VOC设置中的相互作用和行为。5-FU和舒尼替尼显著抑制血管生成芽生并降低细胞活力。值得注意的是，这些药物诱导细胞网络形成发生变化，并破坏患者来源球状体的结构完整性，强调了这些药物在紧密模拟头颈癌肿瘤微环境的模型中的有效性。我们的研究证明了三维血管化肿瘤球微流控芯片作为头颈鳞状细胞癌个性化治疗和研究的有价值工具的潜力。该平台模拟肿瘤微环境，并在评估药物疗效方面具有极高的精度。
