Tumor Cell Targeting and Responsive Nanoplatform for Multimodal-Imaging Guided Chemodynamic/Photodynamic/Photothermal Therapy toward Triple Negative Breast Cancer,ACS Applied Materials & Interfaces

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Tumor Cell Targeting and Responsive Nanoplatform for Multimodal-Imaging Guided Chemodynamic/Photodynamic/Photothermal Therapy toward Triple Negative Breast Cancer
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-06-01 , DOI: 10.1021/acsami.3c04709
Lihong Li _{1,

2,

3} , Jiaojiao Li ₁ , Rongrong Hu ₁ , Xinyu Zhang ₁ , Lei Ding ₁ , Guodong Ren ₁ , Wen Liu _{1,

2} , Haojiang Wang _{1,

2} , Bin Wang ₁ , Chengwu Zhang ₁ , Haipeng Diao _{1,

3}

Affiliation

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with ineffective treatment and poor prognosis. It is in great demand to develop a novel theranostic strategy for accurate diagnosis and targeted treatment of TNBC. In the present study, one nanoplatform (HA-ICG-Fe-PDA), endowed with multimodal imaging-guided chemodynamic/photodynamic/photothermal (CDT/PDT/PTT) synergistic therapy capacity toward TNBC, was innovatively constructed. The nanoplatform was prepared by covalently conjugating ICG-decorated hyaluronic acid (HA) on Fe³⁺-chelated polydopamine (PDA). HA facilitated the targeting and accumulating of the nanoplatform in tumor tissue and cells of TNBC, thus producing enhanced magnetic resonance signal. Upon entering into TNBC cells, the intracellular hyaluronidase-catalyzed cleavage of HA-ICG-Fe-PDA activated the prequenched near-infrared (NIR) fluorescence signal, allowing for the activatable NIR fluorescence imaging. On the other hand, Fe³⁺ in the nanoplatform could be reduced to reactive Fe²⁺ in tumor microenvironment, guaranteeing efficient Fenton reaction-mediated CDT. The combination of ICG with Fe-PDA enhanced the NIR absorption of the nanoplatform so that considerable PTT/PDT and photothermal imaging were achieved under 808 nm laser irradiation. In vitro and in vivo experiments have verified that the proposed nanoplatform integrates the potential of TNBC-targeting, precise NIR fluorescence/magnetic resonance/photothermal trimodal imaging, efficient treatment via synergistic CDT/PDT/PTT, as well as excellent biocompatibility. Therefore, this multifunctional nanoplatform provides a simple and versatile strategy for imaging-guided theranostics of TNBC.

中文翻译：

用于多模态成像引导化学动力学/光动力学/光热治疗三阴性乳腺癌的肿瘤细胞靶向和响应纳米平台

三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，治疗无效，预后差。迫切需要开发一种新的治疗诊断策略来准确诊断和靶向治疗 TNBC。在本研究中，创新地构建了一个纳米平台 (HA-ICG-Fe-PDA)，该平台具有多模式成像引导的化学动力学/光动力学/光热 (CDT/PDT/PTT) 协同治疗 TNBC 的能力。该纳米平台是通过将 ICG 修饰的透明质酸 (HA) 共价结合到 Fe ^{3+上制备的}- 螯合聚多巴胺 (PDA)。HA促进纳米平台在TNBC肿瘤组织和细胞中的靶向和积累，从而产生增强的磁共振信号。进入 TNBC 细胞后，细胞内透明质酸酶催化的 HA-ICG-Fe-PDA 裂解激活预淬灭的近红外 (NIR) 荧光信号，从而实现可激活的 NIR 荧光成像。另一方面，纳米平台中的Fe ³⁺可以在肿瘤微环境中还原为反应性Fe ²⁺，从而保证有效的Fenton反应介导的CDT。ICG 与 Fe-PDA 的结合增强了纳米平台的 NIR 吸收，从而在 808 nm 激光照射下实现了可观的 PTT/PDT 和光热成像。体外和体内实验证实，所提出的纳米平台集成了 TNBC 靶向的潜力、精确的 NIR 荧光/磁共振/光热三峰成像、通过协同 CDT/PDT/PTT 进行的有效治疗，以及出色的生物相容性。因此，这种多功能纳米平台为 TNBC 的成像引导治疗提供了一种简单而通用的策略。

更新日期：2023-06-01

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