Xing Lijun, Yang Xiaoting, Bai Jianhua, Zhong Chunting, Cai Jing, Dan Qing, Ji Yiran, Xu Bingxuan, Yu Keyan, Chen Xiaoyu, Qi Yulong, Li Li, Chen Yun, Shuai Xintao, Cheng Guanxun, Liu Li, Zheng Tingting
Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Institute of Ultrasonic Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, Guangdong, P. R. China.
Department of Hubei University of Medicine, Wuhan 430000, Hubei, P. R. China.
Biomater Sci. 2024 Dec 17;13(1):179-192. doi: 10.1039/d4bm00613e.
Early diagnosis of liver cancer and appropriate treatment options are critical for obtaining a good prognosis. However, due to technical limitations, it is difficult to make an early and accurate diagnosis of liver cancer, and the traditional imaging model is relatively simple. Therefore, we synthesized multifunctional diagnostic/therapeutic nanoparticles, UMFNPs/Ce6@MBs, loaded with ultra-small manganese ferrite nanoparticles (UMFNPs) and chlorin e6 (Ce6). This nanoplatform can take full advantage of hypoxia, acidic pH (acidosis) and increased levels of reactive oxygen species ( HO) in the tumor microenvironment (TME). Specific imaging and drug release can also enhance tumor therapy by modulating the hypoxic state of the TME to achieve the combined effect of sonodynamic therapy and photodynamic therapy (SPDT). In addition, the prepared UMFNPs/Ce6@MBs have HO and pH-sensitive biodegradability and can release UMFNPs and photosensitizer Ce6 in the TME while producing O and Mn. The obtained Mn ion nanoparticles can be used for magnetic resonance imaging of tumor-bearing mice, and the released Ce6 can provide fluorescence imaging function at the same time. Because UMFNPs/Ce6@MB ultrasonic microbubbles show good ultrasonic imaging results, UMFNPs/Ce6@MBs can simultaneously provide multi-modal imaging functions for magnetic resonance imaging (MRI), ultrasound and fluorescence imaging. In conclusion, UMFNPs/Ce6@MBs realize the synergistic treatment of SDT and PDT under multi-mode near-infrared fluorescence imaging and CEUS monitoring, demonstrating its great potential in tumor precision medicine.
肝癌的早期诊断和恰当的治疗方案对于获得良好预后至关重要。然而，由于技术限制，肝癌的早期准确诊断存在困难，且传统成像模型相对简单。因此，我们合成了负载超小锰铁氧体纳米颗粒（UMFNPs）和二氢卟吩e6（Ce6）的多功能诊断/治疗纳米颗粒，即UMFNPs/Ce6@MBs。这种纳米平台能够充分利用肿瘤微环境（TME）中的缺氧、酸性pH值（酸中毒）以及活性氧物种（·OH）水平升高的特点。特定的成像和药物释放还可通过调节TME的缺氧状态来增强肿瘤治疗效果，从而实现声动力疗法和光动力疗法（SPDT）的联合效应。此外，所制备的UMFNPs/Ce6@MBs具有·OH和pH敏感的生物可降解性，能够在TME中释放UMFNPs和光敏剂Ce6，同时产生O和Mn。所获得的锰离子纳米颗粒可用于荷瘤小鼠的磁共振成像，而释放出的Ce6可同时提供荧光成像功能。由于UMFNPs/Ce6@MB超声微泡具有良好的超声成像结果，UMFNPs/Ce6@MBs能够同时为磁共振成像（MRI）、超声和荧光成像提供多模态成像功能。综上所述，UMFNPs/Ce6@MBs在多模态近红外荧光成像和CEUS监测下实现了SDT和PDT协同治疗，展现了其在肿瘤精准医学中的巨大潜力。
