Li Yan, Yin Heng, Gu Kuan, Xu Zhiming, Si Yuhao
School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Traumatology & Orthopedics, Nanjing University of Chinese Medicine Wuxi Affiliated Hospital, Wuxi 214071, China; Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Nanjing University of Chinese Medicine Wuxi Affiliated Hospital, Wuxi, Jiangsu Province 214071, China.
Int J Biol Macromol. 2025 Aug;320(Pt 1):145591. doi: 10.1016/j.ijbiomac.2025.145591. Epub 2025 Jun 26.
Photothermal therapy (PTT) converts light to heat, offering a minimally invasive tumor treatment option. However, its efficacy for triple-negative breast cancer (TNBC) is limited by nanoparticle non-specificity and immunosuppression from tumor-associated macrophages (TAMs). Therefore, it is imperative to develop nanoparticles with high selectivity and precise targeting to enhance the efficacy of tumor treatment. In this study, we developed polyethylene glycol (PEG)- and aptamer (aptPD-L1)-functionalized silver nanotriangles (apt-PNTs) targeting PD-L1-overexpressing tumor cells and TAMs. Subsequently, we evaluated tumor-targeting ability, anti-tumor activity, and TAMs reprogramming effect through in vitro and in vivo studies. The study revealed that the synthesized nanoparticles exhibit exceptional photothermal properties and high stability. The apt-PNTs demonstrate selective uptake by TNBC cells and M2. In murine models, apt-PNTs accumulated maximally in tumors at 6 h. Under near-infrared laser irradiation (40-45 °C), apt-PNTs reduced M2 marker CD206 and increased M1 markers CD16/32 and iNOS, reprogramming TAMs and achieving 68.73 % tumor growth inhibition. In conclusion, in the absence of significant adverse reactions, apt-PNTs exhibit excellent photothermal properties and tumor-targeting ability. This work demonstrates the application of apt-PNTs-mediated PTT in promoting TAMs reprogramming and killing tumors, providing a potential approach for targeted therapy of TNBC.
光热疗法（PTT）可将光转化为热，提供一种微创肿瘤治疗选择。然而，其对三阴性乳腺癌（TNBC）的疗效受到纳米颗粒非特异性以及肿瘤相关巨噬细胞（TAM）免疫抑制的限制。因此，开发具有高选择性和精确靶向性的纳米颗粒以提高肿瘤治疗效果势在必行。在本研究中，我们开发了靶向过表达程序性死亡配体1（PD-L1）的肿瘤细胞和TAM的聚乙二醇（PEG）和适配体（aptPD-L1）功能化的银纳米三角形（apt-PNT）。随后，我们通过体外和体内研究评估了肿瘤靶向能力、抗肿瘤活性和TAM重编程效果。研究表明，合成的纳米颗粒具有出色的光热性能和高稳定性。apt-PNT显示出被TNBC细胞和M2选择性摄取。在小鼠模型中，apt-PNT在6小时时在肿瘤中积累最多。在近红外激光照射（40 - 45°C）下，apt-PNT降低了M2标志物CD206，增加了M1标志物CD16/32和诱导型一氧化氮合酶（iNOS），重编程了TAM并实现了68.73%的肿瘤生长抑制。总之，在无明显不良反应的情况下，apt-PNT具有出色的光热性能和肿瘤靶向能力。这项工作证明了apt-PNT介导的PTT在促进TAM重编程和杀伤肿瘤方面的应用，为TNBC的靶向治疗提供了一种潜在方法。
