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血小板膜包裹的溶瘤痘苗病毒联合吲哚菁绿用于结直肠癌的二次近红外成像引导多模式治疗。

Platelet membrane-coated oncolytic vaccinia virus with indocyanine green for the second near-infrared imaging guided multi-modal therapy of colorectal cancer.

机构信息

The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China; General Surgery, Cancer Center, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China; Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China; Department of Hematology, Hangzhou First People's Hospital, Hangzhou 310003, China.

Department of Joint Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200092, China.

出版信息

J Colloid Interface Sci. 2024 Oct;671:216-231. doi: 10.1016/j.jcis.2024.05.175. Epub 2024 May 23.

DOI:10.1016/j.jcis.2024.05.175
PMID:38801796
Abstract

Colorectal cancer (CRC) is a prevalent malignancy with insidious onset and diagnostic challenges, highlighting the need for therapeutic approaches to enhance theranostic outcomes. In this study, we elucidated the unique temperature-resistant properties of the oncolytic vaccinia virus (OVV), which can synergistically target tumors under photothermal conditions. To capitalize on this characteristic, we harnessed the potential of the OVV by surface-loading it with indocyanine green (ICG) and encapsulating it within a platelet membrane (PLTM), resulting in the creation of PLTM-ICG-OVV (PIOVV). This complex seamlessly integrates virotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT). The morphology, size, dispersion stability, optical properties, and cellular uptake of PIOVV were evaluated using transmission electron microscopy (TEM). In vitro and in vivo experiments revealed specificity of PIOVV for cancer cells; it effectively induced apoptosis and suppressed CT26 cell proliferation. In mouse models, PIOVV exhibits enhanced fluorescence at tumor sites, accompanied by prolonged blood circulation. Under 808 nm laser irradiation, PIOVV significantly inhibited tumor growth. This strategy holds the potential for advancing phototherapy, oncolytic virology, drug delivery, and tumor-specific targeting, particularly in the context of CRC theranostics.

摘要

结直肠癌(CRC)是一种常见的恶性肿瘤,其发病隐匿,诊断困难,这凸显了需要采用治疗方法来提高治疗效果。在这项研究中,我们阐明了溶瘤痘病毒(OVV)的独特耐热特性,OVV 可以在光热条件下协同靶向肿瘤。为了利用这一特性,我们通过在 OVV 表面负载吲哚菁绿(ICG)并将其封装在血小板膜(PLTM)内,从而利用 OVV 的潜力,制造出 PLTM-ICG-OVV(PIOVV)。该复合物无缝集成了病毒疗法、光动力疗法(PDT)和光热疗法(PTT)。我们使用透射电子显微镜(TEM)评估了 PIOVV 的形态、大小、分散稳定性、光学性质和细胞摄取。体外和体内实验表明,PIOVV 对癌细胞具有特异性;它能有效诱导细胞凋亡并抑制 CT26 细胞增殖。在小鼠模型中,PIOVV 在肿瘤部位表现出增强的荧光,同时血液循环时间延长。在 808nm 激光照射下,PIOVV 显著抑制了肿瘤生长。该策略有可能推进光疗、溶瘤病毒学、药物输送和肿瘤特异性靶向治疗,特别是在 CRC 治疗方面。

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