Lee Jae Hee, Lee Chae Gyu, Kim Min Seo, Kim Seungyeob, Song Myoung, Zhang Haohui, Yang Eunbyeol, Kwon Yoon Hee, Jung Young Hoon, Hyeon Dong Yeol, Choi Yoon Ji, Oh Seyong, Joe Daniel J, Kim Taek-Soo, Jeon Sanghun, Huang Yonggang, Kwon Tae-Hyuk, Lee Keon Jae
Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, 60208, USA.
Adv Mater. 2024 Dec 16:e2411494. doi: 10.1002/adma.202411494.
Controlled photooxidation-mediated disruption of collagens in the tumor microenvironment can reduce desmoplasia and enhance immune responsiveness. However, achieving effective light delivery to solid tumors, particularly those with dynamic volumetric changes like pancreatic ductal adenocarcinoma (PDAC), remains challenging and limits the repeated and sustained photoactivation of drugs. Here, 3D, shape-morphing, implantable photonic devices (IPDs) are introduced that enable tumor-specific and continuous light irradiation for effective metronomic photodynamic therapy (mPDT). This IPD adheres seamlessly to the surface of orthotopic PDAC tumors, mitigating issues related to mechanical mismatch, delamination, and internal lesions. In freely moving mouse models, mPDT using the IPD with close adhesion significantly reduces desmoplastic tumor volume without causing cytotoxic effects in healthy tissues. These promising in vivo results underscore the potential of an adaptable and unidirectional IPD design in precisely targeting cancerous organs, suggesting a meaningful advance in light-based therapeutic technologies.
肿瘤微环境中通过可控的光氧化作用破坏胶原蛋白可以减少促结缔组织增生反应并增强免疫反应性。然而,实现向实体瘤有效输送光,尤其是向像胰腺导管腺癌(PDAC)这种具有动态体积变化的肿瘤有效输送光,仍然具有挑战性,并且限制了药物的重复和持续光激活。在此,引入了3D、可变形的植入式光子器件(IPD),其能够实现肿瘤特异性和持续的光照射,以进行有效的节律性光动力疗法(mPDT)。这种IPD可无缝贴合原位PDAC肿瘤的表面,减轻了与机械不匹配、分层和内部损伤相关的问题。在自由活动的小鼠模型中,使用紧密贴合的IPD进行mPDT可显著减小促结缔组织增生性肿瘤的体积,且不会对健康组织产生细胞毒性作用。这些在体内获得的有前景的结果强调了适应性和单向IPD设计在精确靶向癌性器官方面的潜力,表明基于光的治疗技术取得了有意义的进展。