Multifunctional Nanoparticles for Multimodal Imaging-Guided Low-Intensity Focused Ultrasound/Immunosynergistic Retinoblastoma Therapy
Multifunctional Nanoparticles for Multimodal Imaging-Guided Low-Intensity Focused Ultrasound/Immunosynergistic Retinoblastoma Therapy
复制标题
用于多模态成像引导低强度聚焦超声/免疫协同视网膜母细胞瘤治疗的多功能纳米颗粒
DOI：
10.1021/acsami.9b22072
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发表时间：
2020
影响因子：
9.5
通讯作者：
Zhou Xiyuan
中科院分区：
文献类型：
--
作者：
Wang Menglei;Yang Qiming;Li Meng;Zou Hongmi;Wang Zhigang;Ran Haitao;Zheng Yuanyi;Jian Jia;Zhou Yu;Luo Yindeng;Ran Yijun;Jiang Shaoqiu;Zhou Xiyuan
视网膜母细胞瘤（RB）易于延迟诊断或治疗，并且转移的可能性增加。因此，进行有效的影像学检查并提供RB的最佳治疗以防止转移至关重要。支持诊断成像和靶向治疗的纳米颗粒有望非侵入性地整合肿瘤诊断和治疗。在此，我们报告了一种多功能纳米颗粒，用于多模态成像引导的低强度聚焦超声（LIFU）/免疫协同RB治疗。制备了磁性中空介孔金纳米笼（AuNCs）-Fe3O4（AuNCs-Fe3O4）复合纳米粒子，用于包裹胞壁酰二肽（MDP）和全氟戊烷（PFP）。在体外和体内探索了这些纳米颗粒与LIFU结合的多模式成像能力、抗肿瘤作用和树突状细胞（DC）激活能力。并对AuNCs-Fe_3O_4/MDP/PFP的生物安全性进行了系统评价。多功能磁性纳米颗粒增强了体内和体外的光声（PA），超声（US）和磁共振（MR）成像，这有助于诊断和疗效评估。通过磁场在肿瘤中积聚后，纳米颗粒在LIFU照射下发生相变并释放MDP。记录并验证了AuNCs-Fe_3O_4/MDP/PFP和LIFU的组合效应。AuNCs-Fe_3O_4/MDP/PFP增强了LIFU的治疗效果，导致肿瘤的直接凋亡/坏死，而MDP促进了DC的成熟和活化，激活了DC识别和清除肿瘤细胞的能力。通过增强PA/US/MR成像和抑制肿瘤生长，多功能AuNC-Fe3O4/MDP/PFP纳米颗粒显示出巨大的潜力，用于RB的多模式成像引导的LIFU/免疫协同治疗。所提出的纳米平台促进具有高生物安全性的癌症治疗诊断。
Retinoblastoma (RB) is prone to delayed diagnosis or treatment and has an increased likelihood of metastasizing. Thus, it is crucial to perform an effective imaging examination and provide optimal treatment of RB to prevent metastasis. Nanoparticles that support diagnostic imaging and targeted therapy are expected to noninvasively integrate tumor diagnosis and treatment. Herein, we report a multifunctional nanoparticle for multimodal imaging-guided low-intensity focused ultrasound (LIFU)/immunosynergistic RB therapy. Magnetic hollow mesoporous gold nanocages (AuNCs) conjugated with Fe3O4nanoparticles (AuNCs–Fe3O4) were prepared to encapsulate muramyl dipeptide (MDP) and perfluoropentane (PFP). The multimodal imaging capabilities, antitumor effects, and dendritic cell (DC) activation capacity of these nanoparticles combined with LIFU were explored in vitro and in vivo. The biosafety of AuNCs–Fe3O4/MDP/PFP was also evaluated systematically. The multifunctional magnetic nanoparticles enhanced photoacoustic (PA), ultrasound (US), and magnetic resonance (MR) imaging in vivo and in vitro, which was helpful for diagnosis and efficacy evaluation. Upon accumulation in tumors via a magnetic field, the nanoparticles underwent phase transition under LIFU irradiation and MDP was released. A combined effect of AuNCs–Fe3O4/MDP/PFP and LIFU was recorded and verified. AuNCs–Fe3O4/MDP/PFP enhanced the therapeutic effect of LIFU and led to direct apoptosis/necrosis of tumors, while MDP promoted DC maturation and activation and activated the ability of DCs to recognize and clear tumor cells. By enhancing PA/US/MR imaging and inhibiting tumor growth, the multifunctional AuNC–Fe3O4/MDP/PFP nanoparticles show great potential for multimodal imaging-guided LIFU/immunosynergistic therapy of RB. The proposed nanoplatform facilitates cancer theranostics with high biosafety.