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癌细胞膜包覆的舒林酸原酸酯纳米前药用于抑制COX-2表达及化学-光热协同抗肿瘤治疗

Cancer cell membrane-coated sulindac-ortho ester nanoprodrug for inhibiting COX-2 expression and chemo-photothermal synergistic antitumor therapy.

作者信息

Zhang Jingwen, Yang Qirong, Zhang Yiming, Zhang Qide, Wan Yingda, Yan Guoqing, Wang Xin

机构信息

Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province 230601, PR China.

Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui Province 230601, PR China.

出版信息

Int J Pharm. 2025 Apr 15;674:125460. doi: 10.1016/j.ijpharm.2025.125460. Epub 2025 Mar 18.

DOI:10.1016/j.ijpharm.2025.125460
PMID:40112900
Abstract

The paper reported a cancer cell membrane bio-mimetic nanodrug to inhibit the expression of COX-2 in tumor area and realize enhanced chemo-photothermal synergistic anti-tumor effect. Ortho ester bond-coupled sulindac dimer (SU-OE) was first synthesized and co-assembled with doxorubicin to obtain pH-sensitive nanodrug (SU-OE@DOX NPs). Indocyanine green (ICG)-encapsulated H22 cell membrane vesicles (HM) were then co-extruded with SU-OE@DOX NPs to give the bio-mimetic nanoparticles (HM@I/NPs). HM@I/NPs displayed excellent stability and photothermal conversion efficiency. Compared to naked nanoparticles, the cell membrane-coated nanoparticles improved H22 cell uptake through homotypic targeting and effectively reduced internalization of macrophages. In vivo imaging results demonstrated that the nanoparticles could be enriched at tumor site and could raise the temperature of the tumor area to 56.7 °C under NIR laser irradiation. The released SU from HM@I/NPs can inhibit the expression of COX-2, and finally enhanced the chemo-PTT synergistic anti-tumor effect.

摘要

该论文报道了一种癌细胞膜仿生纳米药物,可抑制肿瘤区域COX-2的表达,并实现增强的化疗-光热协同抗肿瘤效果。首先合成了原酸酯键偶联的舒林酸二聚体(SU-OE),并与阿霉素共组装以获得pH敏感纳米药物(SU-OE@DOX NPs)。然后将包裹吲哚菁绿(ICG)的H22细胞膜囊泡(HM)与SU-OE@DOX NPs共挤出,得到仿生纳米颗粒(HM@I/NPs)。HM@I/NPs表现出优异的稳定性和光热转换效率。与裸纳米颗粒相比,细胞膜包被的纳米颗粒通过同源靶向提高了H22细胞摄取,并有效减少了巨噬细胞的内化。体内成像结果表明,纳米颗粒可在肿瘤部位富集,并在近红外激光照射下将肿瘤区域温度升高至56.7℃。从HM@I/NPs释放的SU可抑制COX-2的表达,最终增强化疗-光热疗法协同抗肿瘤效果。

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