Targeted treatment of atherosclerosis with protein–polysaccharide nanoemulsion co-loaded with photosensitiser and upconversion nanoparticles
Targeted treatment of atherosclerosis with protein–polysaccharide nanoemulsion co-loaded with photosensitiser and upconversion nanoparticles
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DOI：
10.1080/1061186x.2023.2284093
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发表时间：
2023-11
影响因子：
4.5
通讯作者：
Jing Huang;Shan Xu;Lina Liu;Jiyuan Zhang;Jinzhuan Xu;Lili Zhang;Xiang Zhou;Lei Huang;Jianqing Peng;Jianing Wang;Zipeng Gong;Yi Chen
中科院分区：
文献类型：
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作者：
Jing Huang;Shan Xu;Lina Liu;Jiyuan Zhang;Jinzhuan Xu;Lili Zhang;Xiang Zhou;Lei Huang;Jianqing Peng;Jianing Wang;Zipeng Gong;Yi Chen
摘要巨噬细胞是动脉粥样硬化(AS)病变中含量最丰富的细胞群，在AS进展的各个阶段都起着至关重要的作用。最近的研究表明，光动力疗法(PDT)产生的活性氧(ROS)可诱导巨噬细胞自噬，从而改善异常的脂代谢和炎症环境。尤其是巨噬细胞来源的泡沫细胞，已成为治疗AS的一种潜在策略。在本研究中，我们制备了葡聚糖(DEX)和牛血清白蛋白(BSA)的结合物(DB)。以DB为乳化剂，制备了上转换纳米粒子(UCNPs)和氯化物e6(Ce6)(UCNPs-Ce6@DB)纳米乳液。修饰在纳米乳液表面的地塞米松能够识别和结合巨噬细胞高表达的清道夫受体A类(SR-A)，并通过SR-A介导的内吞作用促进AS平板中巨噬细胞源性泡沫细胞的摄取。此外，UCNPs-Ce6@DB介导的PDT促进巨噬细胞源性泡沫细胞产生ROS和诱导自噬，增强与胆固醇外流密切相关的蛋白ABCA1的表达，并抑制促炎细胞因子的分泌。最终，UCNPS-Ce6@DB被证明能抑制AS小鼠模型中斑块的形成。总之，UCNPS-Ce6@DB为AS提供了一种有前途的治疗方法。
Abstract Macrophages are the most abundant cell group in atherosclerosis (AS) lesions and play a vital role in all stages of AS progression. Recent research has shown that reactive oxygen species (ROS) generation from photodynamic therapy (PDT) induces macrophage autophagy to improve abnormal lipid metabolism and inflammatory environment. Especially in macrophage-derived foam cells, which has become a potential strategy for the treatment of AS. In this study, we prepared the conjugate (DB) of dextran (DEX) and bovine serum albumin (BSA). The DB was used as the emulsifier to prepare nanoemulsion loaded with upconversion nanoparticles (UCNPs) and chlorin e6 (Ce6) (UCNPs-Ce6@DB). The DEX modified on the surface of the nanoemulsion can recognise and bind to the scavenger receptor class A (SR-A) highly expressed on macrophages and promote the uptake of macrophage-derived foam cells in AS plates through SR-A-mediated endocytosis. In addition, UCNPs-Ce6@DB-mediated PDT enhanced ROS generation and induced autophagy in macrophage-derived foam cells, enhanced the expression of ABCA1, a protein closely related to cholesterol efflux, and inhibited the secretion of pro-inflammatory cytokines. Ultimately, UCNPs-Ce6@DB was shown to inhibit plaque formation in mouse models of AS. In conclusion, UCNPs-Ce6@DB offers a promising treatment for AS.