Butkute Austeja, Kazlauske Evelina, Mlynska Agata, Peciukaityte Emile, Karabanovas Vitalijus, Rotomskis Ricardas, Steponkiene Simona
Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
Life Science Center, Vilnius University, Vilnius, Lithuania.
Int J Nanomedicine. 2025 Aug 8;20:9787-9806. doi: 10.2147/IJN.S518050. eCollection 2025.
Photodynamic therapy (PDT) is a promising tool that utilizes photosensitizers (PS) for two functions: cancer imaging by fluorescence (diagnostics), and treatment by the generation of reactive oxygen species (therapy). Despite its theranostic approach, the efficacy of PDT is often hampered by limited penetration of light into tissues, tumor heterogeneity, and the immunosuppressive tumor microenvironment (TME). Moreover, diagnostics and treatment are activated simultaneously, without the possibility of switching between two processes.
We used photosensitizer chlorin e6 (Ce6) and luminescent quantum dots (QDs) to create a theranostic nanocomplex. Two different light sources were used (980 nm or 650 nm light) to activate either the photoluminescence of quantum dots (QDs) or the generation of singlet oxygen by Ce6. Four distinct CRC cell lines were utilized to represent tumor heterogeneity. The therapeutic efficacy of nanocomplex was assessed in CRC and tumor-associated macrophages (TAMs), a key component of the immunosuppressive TME. Immunomodulatory effects were explored by exposing resident and recruited TAM models to a conditioned medium from PDT-treated CRC cells, followed by gene expression analysis.
Spectral characterization of the QDs-Ce6 nanocomplex demonstrated selective switching between diagnostic and therapeutic modes. Two-photon absorption was activated in QDs by 980 nm laser, thus broadening its excitation capabilities into the infrared region. The nanocomplex accumulated efficiently and uniformly across all CRC cell lines, regardless of their aggressiveness or drug sensitivity. The effect of nanocomplex-assisted PDT was the same among CRC cell lines, contrasting with the variable sensitivity to 5-fluorouracil. Additionally, the PDT caused M2 macrophages to lose their pro-tumor characteristics while potentiating their ability to present antigens. Additionally, M0 macrophages displayed a reduction in immunosuppressive signaling.
The QDs-Ce6 nanocomplex exhibits robust photodynamic cytotoxicity and immunomodulatory potential. These findings highlight the potential of nanocomplex for targeting the aggressive type of tumor cells and the TAM.
光动力疗法（PDT）是一种很有前景的工具，它利用光敏剂（PS）实现两种功能：通过荧光进行癌症成像（诊断）以及通过产生活性氧进行治疗。尽管其具有诊疗一体化的方法，但PDT的疗效常常受到光在组织中穿透有限、肿瘤异质性以及免疫抑制性肿瘤微环境（TME）的阻碍。此外，诊断和治疗同时被激活，无法在两个过程之间切换。
我们使用光敏剂二氢卟吩e6（Ce6）和发光量子点（QDs）创建了一种诊疗纳米复合物。使用两种不同的光源（980nm或650nm光）来激活量子点（QDs）的光致发光或Ce6产生单线态氧。利用四种不同的结直肠癌（CRC）细胞系来代表肿瘤异质性。在CRC和肿瘤相关巨噬细胞（TAM，免疫抑制性TME的关键组成部分）中评估纳米复合物的治疗效果。通过将常驻和募集的TAM模型暴露于经PDT处理的CRC细胞的条件培养基中，然后进行基因表达分析来探索免疫调节作用。
QDs-Ce6纳米复合物的光谱表征证明了在诊断和治疗模式之间的选择性切换。980nm激光激活了量子点中的双光子吸收，从而将其激发能力扩展到红外区域。纳米复合物在所有CRC细胞系中高效且均匀地积累，无论它们的侵袭性或药物敏感性如何。纳米复合物辅助的PDT在CRC细胞系中的效果相同，这与对5-氟尿嘧啶的可变敏感性形成对比。此外，PDT使M2巨噬细胞失去其促肿瘤特性，同时增强其呈递抗原的能力。此外，M0巨噬细胞显示出免疫抑制信号的减少。
QDs-Ce6纳米复合物表现出强大的光动力细胞毒性和免疫调节潜力。这些发现突出了纳米复合物靶向侵袭性肿瘤细胞和TAM的潜力。
