联合UTMD-纳米平台用于有效药物递送以治疗肾细胞癌

Combined UTMD-Nanoplatform for the Effective Delivery of Drugs to Treat Renal Cell Carcinoma

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International Journal of Nanomedicine

影响因子:6.5

分区:医学2区 / 药学2区纳米科技3区

发表日期:2024

作者: Ting Dai, Qimeihui Wang, Lingyu Zhu, Qiang Luo, Jiayu Yang, Xia Meng, Hui Wang, Zhixia Sun

DOI: 10.2147/IJN.S459960

摘要

纳米颗粒（NPs）在肿瘤区域的有效积累是当前纳米技术研究的重要目标，而靶向纳米平台则是一种有效的解决方案。因此，我们设计了一种多功能声敏感靶向NP，结合声敏化剂以实现精确靶向、深层穿透的声动力学疗法（SDT），并结合多模态成像用于肾细胞癌（RCC）的诊断和监测。ZnPP@PP NPs（ZnPP@PLGA-PFP NPs）通过双乳化法制备，G250通过碳酰二胺法共价连接到NPs壳体。对ZnPP@G-PP NPs进行了理化性质检测，包括粒径、潜在分布、包封效率和药物负载能力。在体外评估了NP的靶向能力、活性氧（ROS）产生和渗透性。此外，还评估了NP的多模态成像能力和对RCC的治疗效果，包括体外和体内实验。ZnPP@G-PP NPs成功构建，其一般性质表现为粒径均一、负电位和良好的稳定性。成功加载ZnPP并与G250连接，显示出肿瘤特异性靶向能力。在LIFU照射下，NP通过SDT产生1O2。对于RCC，ZnPP@G-PP NPs在786-O RCC异种移植模型中实现了PA/US多模态成像，提供诊断信息并实时监测治疗，且具有良好的生物相容性。借助UTMD，NP能够有效靶向肿瘤细胞并穿透肿瘤内部，显著提高SDT效果。体外和体内实验均显示，NP与LIFU联合能够抑制肿瘤，且治疗效果通过免疫组化确认。ZnPP@G-PP NPs为RCC提供了一种具有潜力的治疗-诊断策略，并为进一步研究提高诊断和治疗效果的平台提供基础。

Abstract

The effective accumulation of nanoparticles (NPs) in the tumour area is an important goals of current nanotechnology research, and a targeted nanoplatform is an effective solution. So we designed a multifunctional sound-sensitive targeted NP that combines a sonosensitizer to enable precisely targeted, deep-penetration sonodynamic therapy (SDT) in combination with multimodal imaging for the diagnosis and monitoring of renal cell carcinoma (RCC).ZnPP@PP NPs (ZnPP@PLGA- PFP NPs) were prepared via a double emulsion method, and G250 was covalently attached to the NPs shell via the carbon diimide method. Physicochemical property tests were conducted on the ZnPP@G-PP NPs, including tests of particle size, potential distribution, encapsulation efficiency and drug loading capability. We assessed the targeting ability, the production of reactive oxygen species (ROS) and permeability of the NPs in vitro. Moreover, we evaluated the nanoparticle's multimodal imaging capabilities and therapeutic ability against RCC, both in vitro and in vivo.The Znpp@G-PP NPs were successfully constructed, and their general properties showed uniform particle size, negative potential and good stability. The nanoparticles were successfully loaded with ZnPP and connected with G250, showing tumor-specific targeting ability. Under LIFU irradiation, the nanoparticles produced 1O2 by SDT. For RCC, PA/US multi-modal imaging of Znpp@G-PP NPs provide diagnostic information and monitor therapies in real time in 786-O RCC xenografts, with good biocompatibility. With the UTMD, nanoparticles can be effectively targeted into the tumor cells and penetrate into the tumor interior, significantly improving the SDT effect. Experiments in vitro and in vivo showed that the combination of the nanoparticles and LIFU could suppress the tumor, and the therapeutic effect was confirmed by immunohistochemistry.ZnPP@G-PP NPs provide a promising theranostic strategy for RCC and a platform for further research on improving the efficacy of diagnosis and treatment.