Takahashi Masataka, Fujishiro Jun, Nomura Shinsuke, Harada Manabu, Hinoki Akinari, Arake Masashi, Ozeki Eiichi, Hara Isao, Satoh Ayano, Tainaka Takahisa, Uchida Hiro-O, Morimoto Yuji
Department of Pediatric Surgery, The University of Tokyo, Tokyo, Japan.
Department of Cell Engineering, National Center for Child Health and Development, Tokyo, Japan.
Front Bioeng Biotechnol. 2024 Aug 15;12:1444107. doi: 10.3389/fbioe.2024.1444107. eCollection 2024.
The efficacy of drug delivery system (DDS)-type near-infrared (NIR) absorbing agents in enhancing laser photothermal therapy is widely acknowledged. Despite the acknowledged efficacy, the therapeutic advantages of photothermal therapy using DDS-type NIR-absorbing agents over simple photothermal therapy without such agents have not been fully elucidated. This study was designed to investigate two primary objectives: firstly, the ability of DDS-type NIR-absorbing agents to induce cell death at greater depths within tumors, and secondly, their capacity to minimize collateral damage to adjacent healthy organs. To investigate these objectives, we employed a combination of indocyanine green lactosome-a DDS-type NIR-absorbing agent-and a precision-controlled laser hyperthermia system. An orthotopic neuroblastoma tumor model was used to closely simulate clinical conditions. The findings revealed that photothermal therapy using the DDS-type NIR-absorbing agent not only facilitates deeper penetration of cell death within tumors but also significantly mitigates thermal damage to surrounding healthy tissues, when compared to simple phototherapy without the agent. Furthermore, the combined treatment significantly prolonged the survival periods of the animals involved. This study is the first to analyze these therapeutic efficacies using quantitative data from an orthotopic tumor animal model and substantiated the potential of DDS-type NIR-absorbing agents to deepen the therapeutic impact of photothermal therapy while safeguarding vital organs, thereby enhancing overall treatment outcomes.
药物递送系统(DDS)型近红外(NIR)吸收剂在增强激光光热疗法方面的疗效已得到广泛认可。尽管疗效得到公认,但使用DDS型NIR吸收剂的光热疗法相对于不使用此类吸收剂的单纯光热疗法的治疗优势尚未得到充分阐明。本研究旨在调查两个主要目标:第一,DDS型NIR吸收剂在肿瘤更深层诱导细胞死亡的能力;第二,它们将对相邻健康器官的附带损害降至最低的能力。为了研究这些目标,我们采用了吲哚菁绿脂质体(一种DDS型NIR吸收剂)和精密控制的激光热疗系统相结合的方法。使用原位神经母细胞瘤肿瘤模型来密切模拟临床情况。研究结果表明,与不使用该吸收剂的单纯光疗相比,使用DDS型NIR吸收剂的光热疗法不仅有助于在肿瘤内更深入地诱导细胞死亡,而且还能显著减轻对周围健康组织的热损伤。此外,联合治疗显著延长了相关动物的生存期。本研究首次使用原位肿瘤动物模型的定量数据来分析这些治疗效果,并证实了DDS型NIR吸收剂在加深光热疗法的治疗效果同时保护重要器官从而提高整体治疗效果方面的潜力。