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共负载索拉非尼和金纳米颗粒的肿瘤源性微粒对肝癌的放射增敏作用

The Radiosensitizing Effect of Tumor-Derived Microparticles Co-Loaded with Sorafenib and Gold Nanoparticles on Hepatocellular Carcinoma.

作者信息

Yu Li, Liu Jiali, Fan Yiwen, Hu Xiao, Zeng Xiaonan, Luo Shan, Chen Ping

机构信息

Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

Department of Oncology, Jiangsu Cancer Hospital, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, 210009, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Apr 28;20:5489-5508. doi: 10.2147/IJN.S509936. eCollection 2025.

Abstract

OBJECTIVE

Hepatocellular carcinoma (HCC) is a highly heterogeneous tumor with features such as high recurrence, easy metastasis, and poor prognosis, posing significant challenges for clinical treatment. In this study, we introduce a novel approach for treating HCC using tumor cell-derived microparticles (MPs) co-loaded with sorafenib and gold nanoparticles (AuNP) in combination with radiotherapy.

METHODS

MPSF@AuNP was prepared by co-incubating AuNP with sorafenib, and was evaluated using dynamic light scattering (DLS), transmission electron microscopy (TEM), ultraviolet-visible spectrophotometry (UV-Vis), inductively coupled plasma optical emission spectrometry (ICP-OES), high-performance liquid chromatography (HPLC), and SDS-PAGE electrophoresis. Subsequently, their targeting ability toward hepatocellular carcinoma cells and their combined antitumor therapeutic effects with radiotherapy were investigated through in vitro and in vivo experiments, while their in vivo safety was also assessed.

RESULTS

Our results demonstrate that co-loaded microparticles (MPSF@AuNP) can effectively deliver therapeutic agents to tumor cells through homologous targeting, improving the bioavailability of therapeutic drugs and enhancing their cytotoxicity against tumor cells. Furthermore, the combination of MPSF@AuNP with radiotherapy shows a synergistic anti-tumor effect by enhancing the inhibition of tumor cell proliferation, promoting tumor cell apoptosis, remodeling the tumor microenvironment, and activating the anti-tumor immune responses.

CONCLUSION

This study offers a promising treatment approach for malignant tumors such as HCC by using MP co-loaded and delivered with anti-tumor drugs and AuNP in combination with radiotherapy.

摘要

目的

肝细胞癌(HCC)是一种高度异质性肿瘤,具有高复发、易转移和预后差等特点,给临床治疗带来重大挑战。在本研究中,我们引入了一种新的治疗HCC的方法,即使用同时负载索拉非尼和金纳米颗粒(AuNP)的肿瘤细胞衍生微粒(MPs)联合放射治疗。

方法

通过将AuNP与索拉非尼共同孵育制备MPSF@AuNP,并使用动态光散射(DLS)、透射电子显微镜(TEM)、紫外可见分光光度法(UV-Vis)、电感耦合等离子体发射光谱法(ICP-OES)、高效液相色谱法(HPLC)和SDS-PAGE电泳进行评估。随后,通过体外和体内实验研究它们对肝癌细胞的靶向能力以及与放射治疗联合的抗肿瘤治疗效果,同时评估其体内安全性。

结果

我们的结果表明,共负载微粒(MPSF@AuNP)可以通过同源靶向有效地将治疗剂递送至肿瘤细胞,提高治疗药物的生物利用度并增强其对肿瘤细胞的细胞毒性。此外,MPSF@AuNP与放射治疗的联合通过增强对肿瘤细胞增殖的抑制、促进肿瘤细胞凋亡、重塑肿瘤微环境和激活抗肿瘤免疫反应,显示出协同抗肿瘤作用。

结论

本研究通过使用负载并递送抗肿瘤药物和AuNP的MP联合放射治疗,为HCC等恶性肿瘤提供了一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11a5/12047280/9d4b38c39864/IJN-20-5489-g0001.jpg

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