Atherosclerosis (AS), a chronic vascular inflammatory disease characterized by scattered and deep-seated lesions, is a major cause of cardiovascular disease. Efficient drug delivery is crucial for enhancing therapeutic efficacy in this condition. Nanomaterials exhibit significant advantages in drug delivery systems owing to their unique physicochemical properties. Through targeted surface functionalization, they enable precise drug targeting, promote enhanced accumulation at pathological sites, reduce off-target biodistribution, and ultimately improve both therapeutic efficacy and safety profiles. Nano-delivery systems, categorized based on material characteristics into four major classes—lipid-based, polymeric, inorganic, and biomimetic nanocarriers—have multifunctional composite designs that support multimodal synergistic therapies (e.g., photothermal conversion and magnetic-responsive imaging-guided therapy). These approaches hold significant potential for enhancing therapeutic efficiency in AS management. This review synthesizes recent advances in nanocarrier-based strategies for AS management, focusing on the synthesis of diverse nanocarrier types, targeting mechanisms, and multimodal applications. It covers representative achievements ranging from basic research to preclinical studies and partial clinical trials, while outlining future development directions for nanotechnology-based therapeutic strategies and providing critical perspectives on technical innovations and persistent translational hurdles in this field.
脂质体是由双亲性磷脂分子通过分子间疏水作用自发形成的囊泡结构，可呈现出单室或多室形态。其拥有卓越的荷载能力，可同时兼容亲水、疏水及亲脂性药物分子。该递送系统的体外和体内稳定性受多重参数协同影响，包括粒径分布范围、表面电荷性质、膜材组成配比以及表面功能化修饰策略，而这些关键参数均可在制备过程中进行调控。脂质体可通过膜融合机制实现其负载物的胞内递送，这一过程使活性成分直接释放至细胞质以发挥疗效。研究［7］表明，经表面修饰的脂质体还能触发细胞通过能量依赖型内吞途径完成外源物质的跨膜运输。脂质体还可以作为基因转运系统，通过物理包埋或表面吸附的方式有效荷载DNA和RNA分子，为基因治疗及基因编辑提供精准递送。HO等［8］设计并制备了一种阳离子脂质体用于miR-146a（microRNA 146a）递送。相较游离miR-146a，脂质体复合物显著提升稳定性与细胞转染效率，并有效抑制内皮细胞及平滑肌细胞异常激活，减少促炎症因子分泌及泡沫细胞形成。当前脂质体技术已突破传统结构局限，发展为新一代精准调控系统。该系统通过多功能化设计，结合配体修饰与膜材组分协同调控，在保留脂质双层结构的同时，显著提升了靶向递送效率与制剂均一性［9-10］。脂质体纳米载体发展较快，已有部分进入临床实验阶段，VAN DER VALK团队［11］首次在动脉粥样硬化患者中开展了使用包裹泼尼松龙的长循环脂质体纳米颗粒的临床试验，研究结果表明动脉壁通透性未见明显改善，血脂和炎症水平在治疗前后亦无显著变化，但该结果为未来纳米药物在心血管疾病领域的发展确定了起点。
金纳米粒子（gold nanoparticle，AuNP）作为典型的金属纳米材料，其金属特性与尺寸形貌调控协同赋予其独特光热转换性能，为生物医学应用提供多种可能。其合成过程高度可控，支持药物装载需求，结合高比表面积及表面化学可修饰性，既能高效负载抗动脉粥样硬化药物，又可通过功能化设计实现多组分协同递送，构建多功能集成纳米系统［26-28］。LEE研究团队［29］系统评估了荧光金纳米簇（fluorescent gold nanoclusters，FANC）对动脉粥样硬化进展的干预效能。发现其通过多靶点机制改善病理特征：①显著减轻主动脉病变，降低血清胆固醇及氧化应激标志物［丙二醛、4-羟基壬烯醛（4-hydroxynonenal，4-HNE）］水平。②肝脏分析显示缓解脂质沉积并调控脂质代谢基因［3-羟基-3-甲基戊二酸单酰辅酶A还原酶（3-hydroxy-3-methyl glutaryl coenzyme A reductase，HMGCR）、固醇调节元件结合蛋白（sterol regulatory element binding protein 2，SREBP）、前蛋白转化酶枯草杆菌蛋白酶（proprotein convertase subtilisin-kexin type 9，PCSK9）、低密度脂蛋白受体（low density lipoprotein receptor，LDLR）］表达。③肠道胆固醇吸收抑制活性与药物依泽替米贝相当。研究表明FANC通过多机制协同发挥抗动脉粥样硬化作用。KHARLAMOV团队［30］采用硅-金纳米颗粒对患者进行血浆光热疗法，结果表明患者动脉粥样硬化斑块体积和坏死核心减少，冠状动脉舒张功能增强，心血管死亡率降低。
CHEN Liang was responsible for literature review, drafting the initial manuscript, and completing revisions. WU Biao was responsible for the revision of the paper. YUAN Liangxi was responsible for providing writing guidance and reviewing the paper. All authors have read the final version of paper and consented to the submission.
利益冲突声明
所有作者声明不存在利益冲突。
Conflict of Interests
All authors declare no relevant conflict of interests.
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... 金纳米粒子（gold nanoparticle，AuNP）作为典型的金属纳米材料，其金属特性与尺寸形貌调控协同赋予其独特光热转换性能，为生物医学应用提供多种可能.其合成过程高度可控，支持药物装载需求，结合高比表面积及表面化学可修饰性，既能高效负载抗动脉粥样硬化药物，又可通过功能化设计实现多组分协同递送，构建多功能集成纳米系统［26-28］.LEE研究团队［29］系统评估了荧光金纳米簇（fluorescent gold nanoclusters，FANC）对动脉粥样硬化进展的干预效能.发现其通过多靶点机制改善病理特征：①显著减轻主动脉病变，降低血清胆固醇及氧化应激标志物［丙二醛、4-羟基壬烯醛（4-hydroxynonenal，4-HNE）］水平.②肝脏分析显示缓解脂质沉积并调控脂质代谢基因［3-羟基-3-甲基戊二酸单酰辅酶A还原酶（3-hydroxy-3-methyl glutaryl coenzyme A reductase，HMGCR）、固醇调节元件结合蛋白（sterol regulatory element binding protein 2，SREBP）、前蛋白转化酶枯草杆菌蛋白酶（proprotein convertase subtilisin-kexin type 9，PCSK9）、低密度脂蛋白受体（low density lipoprotein receptor，LDLR）］表达.③肠道胆固醇吸收抑制活性与药物依泽替米贝相当.研究表明FANC通过多机制协同发挥抗动脉粥样硬化作用.KHARLAMOV团队［30］采用硅-金纳米颗粒对患者进行血浆光热疗法，结果表明患者动脉粥样硬化斑块体积和坏死核心减少，冠状动脉舒张功能增强，心血管死亡率降低. ...
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... 金纳米粒子（gold nanoparticle，AuNP）作为典型的金属纳米材料，其金属特性与尺寸形貌调控协同赋予其独特光热转换性能，为生物医学应用提供多种可能.其合成过程高度可控，支持药物装载需求，结合高比表面积及表面化学可修饰性，既能高效负载抗动脉粥样硬化药物，又可通过功能化设计实现多组分协同递送，构建多功能集成纳米系统［26-28］.LEE研究团队［29］系统评估了荧光金纳米簇（fluorescent gold nanoclusters，FANC）对动脉粥样硬化进展的干预效能.发现其通过多靶点机制改善病理特征：①显著减轻主动脉病变，降低血清胆固醇及氧化应激标志物［丙二醛、4-羟基壬烯醛（4-hydroxynonenal，4-HNE）］水平.②肝脏分析显示缓解脂质沉积并调控脂质代谢基因［3-羟基-3-甲基戊二酸单酰辅酶A还原酶（3-hydroxy-3-methyl glutaryl coenzyme A reductase，HMGCR）、固醇调节元件结合蛋白（sterol regulatory element binding protein 2，SREBP）、前蛋白转化酶枯草杆菌蛋白酶（proprotein convertase subtilisin-kexin type 9，PCSK9）、低密度脂蛋白受体（low density lipoprotein receptor，LDLR）］表达.③肠道胆固醇吸收抑制活性与药物依泽替米贝相当.研究表明FANC通过多机制协同发挥抗动脉粥样硬化作用.KHARLAMOV团队［30］采用硅-金纳米颗粒对患者进行血浆光热疗法，结果表明患者动脉粥样硬化斑块体积和坏死核心减少，冠状动脉舒张功能增强，心血管死亡率降低. ...
1
... 金纳米粒子（gold nanoparticle，AuNP）作为典型的金属纳米材料，其金属特性与尺寸形貌调控协同赋予其独特光热转换性能，为生物医学应用提供多种可能.其合成过程高度可控，支持药物装载需求，结合高比表面积及表面化学可修饰性，既能高效负载抗动脉粥样硬化药物，又可通过功能化设计实现多组分协同递送，构建多功能集成纳米系统［26-28］.LEE研究团队［29］系统评估了荧光金纳米簇（fluorescent gold nanoclusters，FANC）对动脉粥样硬化进展的干预效能.发现其通过多靶点机制改善病理特征：①显著减轻主动脉病变，降低血清胆固醇及氧化应激标志物［丙二醛、4-羟基壬烯醛（4-hydroxynonenal，4-HNE）］水平.②肝脏分析显示缓解脂质沉积并调控脂质代谢基因［3-羟基-3-甲基戊二酸单酰辅酶A还原酶（3-hydroxy-3-methyl glutaryl coenzyme A reductase，HMGCR）、固醇调节元件结合蛋白（sterol regulatory element binding protein 2，SREBP）、前蛋白转化酶枯草杆菌蛋白酶（proprotein convertase subtilisin-kexin type 9，PCSK9）、低密度脂蛋白受体（low density lipoprotein receptor，LDLR）］表达.③肠道胆固醇吸收抑制活性与药物依泽替米贝相当.研究表明FANC通过多机制协同发挥抗动脉粥样硬化作用.KHARLAMOV团队［30］采用硅-金纳米颗粒对患者进行血浆光热疗法，结果表明患者动脉粥样硬化斑块体积和坏死核心减少，冠状动脉舒张功能增强，心血管死亡率降低. ...
1
... 金纳米粒子（gold nanoparticle，AuNP）作为典型的金属纳米材料，其金属特性与尺寸形貌调控协同赋予其独特光热转换性能，为生物医学应用提供多种可能.其合成过程高度可控，支持药物装载需求，结合高比表面积及表面化学可修饰性，既能高效负载抗动脉粥样硬化药物，又可通过功能化设计实现多组分协同递送，构建多功能集成纳米系统［26-28］.LEE研究团队［29］系统评估了荧光金纳米簇（fluorescent gold nanoclusters，FANC）对动脉粥样硬化进展的干预效能.发现其通过多靶点机制改善病理特征：①显著减轻主动脉病变，降低血清胆固醇及氧化应激标志物［丙二醛、4-羟基壬烯醛（4-hydroxynonenal，4-HNE）］水平.②肝脏分析显示缓解脂质沉积并调控脂质代谢基因［3-羟基-3-甲基戊二酸单酰辅酶A还原酶（3-hydroxy-3-methyl glutaryl coenzyme A reductase，HMGCR）、固醇调节元件结合蛋白（sterol regulatory element binding protein 2，SREBP）、前蛋白转化酶枯草杆菌蛋白酶（proprotein convertase subtilisin-kexin type 9，PCSK9）、低密度脂蛋白受体（low density lipoprotein receptor，LDLR）］表达.③肠道胆固醇吸收抑制活性与药物依泽替米贝相当.研究表明FANC通过多机制协同发挥抗动脉粥样硬化作用.KHARLAMOV团队［30］采用硅-金纳米颗粒对患者进行血浆光热疗法，结果表明患者动脉粥样硬化斑块体积和坏死核心减少，冠状动脉舒张功能增强，心血管死亡率降低. ...
