Lee Kyung Kwan, Park Kyung-Woo, Lee Sang Cheon, Lee Chang-Soo
Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Department of Maxillofacial Biomedical Engineering, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
Theranostics. 2025 Jan 1;15(3):1077-1093. doi: 10.7150/thno.102743. eCollection 2025.
Activatable multifunctional nanoparticles present considerable advantages in cancer treatment by integrating both diagnostic and therapeutic functionalities into a single platform. These nanoparticles can be precisely engineered to selectively target cancer cells, thereby reducing the risk of damage to healthy tissues. Once localized at the target site, they can be activated by external stimuli such as light, pH changes, or specific enzymes, enabling precise control over the release of therapeutic agents or the initiation of therapeutic effects. Furthermore, these nanoparticles can be designed to incorporate multiple therapeutic modalities, including chemotherapy, photothermal therapy (PTT), and chemodynamic therapy (CDT). This comprehensive approach facilitates real-time monitoring of treatment efficacy and allows for dynamic adjustments to therapy, resulting in more personalized and effective cancer treatments. This study reports the synthesis of perfluorocarbon (PFC)-encapsulated fluorescent polyepinephrine (PEPP) nanoshells chelated with Fe (PFC@PEPP-Fe) and explores their potential for bimodal imaging and synergistic combination therapy in cancer treatment. The cellular uptake, cytotoxicity, and therapeutic efficacy of PFC@PEPP-Fe were assessed using 4T1 breast cancer cells. bimodal imaging using fluorescence (FL) and ultrasound (US) was conducted after injection into 4T1 tumor-bearing balb/c nude mice. The synergistic anticancer effects of PFC@PEPP-Fe, combining CDT and PTT, were evaluated following 808 nm laser irradiation (1 W/cm²) for 5 min, with treatment outcomes monitored over a 14 days period. Both and studies demonstrated that PFC@PEPP-Fe enables effective bimodal imaging and exhibits substantial anticancer efficacy through the synergistic effects of PTT and CDT. Near-infrared (NIR) laser irradiation increased the temperature, enhancing the release of O and the production of HO, which in turn amplified the CDT effect. The combination of PFC@PEPP-Fe administration and NIR laser significantly reduced tumor volume, slowed tumor growth, and improved survival in 4T1 tumor-bearing mice, confirming the strong anticancer activity due to the PTT/CDT synergy. As a multifunctional theranostic nanoparticle, PFC@PEPP-Fe not only enables cancer cell-specific US/FL bimodal imaging through the generation of microbubbles from its PFC core and fluorescent PEPP shells but also facilitates synergistic chemodynamic and photothermal therapeutic actions under NIR laser irradiation, which induces the self-supply of HO and O within cancer cells.
可激活的多功能纳米粒子通过将诊断和治疗功能整合到一个单一平台，在癌症治疗中具有显著优势。这些纳米粒子可以经过精确设计以选择性地靶向癌细胞，从而降低对健康组织造成损伤的风险。一旦定位在靶位点，它们可以被诸如光、pH变化或特定酶等外部刺激激活，实现对治疗剂释放或治疗效果启动的精确控制。此外，这些纳米粒子可以设计成包含多种治疗方式，包括化疗、光热疗法（PTT）和化学动力学疗法（CDT）。这种综合方法有助于实时监测治疗效果，并允许对治疗进行动态调整，从而实现更个性化和有效的癌症治疗。本研究报道了合成与铁螯合的全氟碳（PFC）包裹的荧光聚肾上腺素（PEPP）纳米壳（PFC@PEPP-Fe），并探索了它们在癌症治疗中进行双模态成像和协同联合治疗的潜力。使用4T1乳腺癌细胞评估了PFC@PEPP-Fe的细胞摄取、细胞毒性和治疗效果。将其注射到荷4T1肿瘤的balb/c裸鼠体内后，进行了荧光（FL）和超声（US）双模态成像。在808 nm激光照射（1 W/cm²）5分钟后，评估了结合CDT和PTT的PFC@PEPP-Fe的协同抗癌效果，并在14天内监测治疗结果。两项研究均表明，PFC@PEPP-Fe能够实现有效的双模态成像，并通过PTT和CDT的协同作用展现出显著的抗癌效果。近红外（NIR）激光照射提高了温度，增强了O的释放和HO的产生，进而放大了CDT效果。给予PFC@PEPP-Fe并结合NIR激光显著减小了荷4T1肿瘤小鼠的肿瘤体积，减缓了肿瘤生长，并提高了生存率，证实了由于PTT/CDT协同作用而产生的强大抗癌活性。作为一种多功能诊疗纳米粒子，PFC@PEPP-Fe不仅通过其PFC核心产生微泡和荧光PEPP壳实现癌细胞特异性的US/FL双模态成像，还在NIR激光照射下促进协同化学动力学和光热治疗作用，这会诱导癌细胞内HO和O的自我供应。
