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超声/磁共振双模态成像引导的CD20靶向多功能纳米平台用于B细胞淋巴瘤的光热/化疗协同治疗

Ultrasound/magnetic resonance bimodal imaging-guided CD20-targeted multifunctional nanoplatform for photothermal/chemo synergistic therapy of B-cell lymphoma.

作者信息

Wang Zhengji, Huang Jian, Lv Weiyang, Huang Chunxin, Wang Ying, Li Xing, Liu Huilin, Hao Liguo

机构信息

Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, China.

Department of Ultrasound, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

出版信息

J Pharm Sci. 2025 Feb;114(2):967-982. doi: 10.1016/j.xphs.2024.11.004. Epub 2024 Nov 16.

DOI:10.1016/j.xphs.2024.11.004
PMID:39551237
Abstract

B-cell lymphoma has a poor prognosis due to difficulties in early diagnosis and the negative effects of systemic chemotherapy. Therefore, there is an urgent need to develop highly accurate and effective theranostic strategies for B-cell lymphoma. In this study, we designed a poly (lactic-co-glycolic acid) (PLGA)-based theranostic nanoplatform (denoted as TscNPs) to achieve ultrasound (US)/magnetic resonance (MR) bimodal imaging-guided photothermal (PTT)/chemo synergistic therapy of B-cell lymphoma. The nanoplatform was conjugated with a CD20 monoclonal antibody specifically targeting B-cell lymphoma to promote tumor accumulation. Encapsulated superparamagnetic iron oxide nanoparticles (SPIONs) as photothermal and MR imaging agents enabled thermal ablation of tumors and imaging-guided tumor therapy. When exposed to near-infrared (NIR) laser, TscNPs generate heat that induces optical droplet vaporization (ODV) of perfluoropentane (PFP), which transforms into microbubbles. This process not only enhanced ultrasound imaging, but also facilitated the release of celastrol (CST) from the nanoplatform, ultimately achieving a PTT/chemo synergistic therapy effect. In the tumor-bearing nude mice model, TscNPs were effectively accumulated in the tumor region. Furthermore, the combined treatment mode of TscNPs and NIR laser irradiation demonstrated a tumor inhibition rate of approximately 96.57 %, which was significantly superior to the rates observed with PTT or chemotherapy alone. These results suggest that the multifunctional theranostic nanoplatform represents a promising new strategy for the therapy of B-cell lymphoma.

摘要

由于早期诊断困难以及全身化疗的负面影响,B细胞淋巴瘤的预后较差。因此,迫切需要开发针对B细胞淋巴瘤的高度准确且有效的诊疗策略。在本研究中,我们设计了一种基于聚乳酸-乙醇酸共聚物(PLGA)的诊疗纳米平台(称为TscNPs),以实现超声(US)/磁共振(MR)双模态成像引导的B细胞淋巴瘤光热(PTT)/化疗协同治疗。该纳米平台与特异性靶向B细胞淋巴瘤的CD20单克隆抗体偶联,以促进肿瘤蓄积。封装的超顺磁性氧化铁纳米颗粒(SPIONs)作为光热和MR成像剂,能够实现肿瘤的热消融以及成像引导的肿瘤治疗。当暴露于近红外(NIR)激光时,TscNPs产生热量,诱导全氟戊烷(PFP)发生光滴汽化(ODV),进而转化为微泡。这一过程不仅增强了超声成像,还促进了雷公藤红素(CST)从纳米平台的释放,最终实现PTT/化疗协同治疗效果。在荷瘤裸鼠模型中,TscNPs有效地蓄积在肿瘤区域。此外,TscNPs与NIR激光照射的联合治疗模式显示出约96.57%的肿瘤抑制率,显著优于单独使用PTT或化疗时观察到的抑制率。这些结果表明,多功能诊疗纳米平台是治疗B细胞淋巴瘤的一种有前景的新策略。

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