基于纳米材料的递送系统在动脉粥样硬化诊疗中的应用进展

doi:10.3969/j.issn.1674-8115.2025.12.015

摘要/Abstract

摘要：

动脉粥样硬化是一种慢性血管炎症，其病灶分散且位置深在，是心血管疾病发病的主要原因。高效的药物递送是提升其治疗效果的关键要素。纳米材料凭借其独特的理化特性，在药物递送中优势显著，通过功能化修饰可实现靶向递送，增强药物在病变部位的富集，减少脱靶分布，提高治疗安全性与有效性。纳米递送系统按材料特性可分为脂基纳米载体、聚合物纳米载体、无机纳米载体和仿生纳米载体四大类，其多功能复合体系设计更支持多模态协同治疗，如光热转换、磁响应成像引导治疗等，对提高动脉粥样硬化治疗效率具有重要意义。该文系统梳理了纳米载体在动脉粥样硬化治疗中的应用研究进展，重点探讨不同类型纳米载体的构建、靶向机制及多模态应用，涵盖了从基础研究到临床前及部分临床实验的代表性成果，并展望未来基于纳米技术的治疗策略发展方向，以期为该领域的进一步研究与临床转化提供参考。

关键词: 纳米材料, 纳米技术, 动脉粥样硬化

Abstract:

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.

Key words: nanomaterial, nanotechnology, atherosclerosis

中图分类号:

R543.5

陈亮, 吴彪, 袁良喜. 基于纳米材料的递送系统在动脉粥样硬化诊疗中的应用进展[J]. 上海交通大学学报（医学版）, 2025, 45(12): 1687-1693.

CHEN Liang, WU Biao, YUAN Liangxi. Application progress of nanomaterial-based delivery systems in atherosclerosis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(12): 1687-1693.

图/表 1

参考文献 56

[1]	HETHERINGTON I, TOTARY-JAIN H. Anti-atherosclerotic therapies: milestones, challenges, and emerging innovations[J]. Mol Ther, 2022, 30(10): 3106-3117.
[2]	MUSHENKOVA N V, SUMMERHILL V I, ZHANG D W, et al. Current advances in the diagnostic imaging of atherosclerosis: insights into the pathophysiology of vulnerable plaque[J]. Int J Mol Sci, 2020, 21(8): 2992.
[3]	NEWMAN C B, PREISS D, TOBERT J A, et al. Statin safety and associated adverse events: a scientific statement from the American Heart Association[J]. Arterioscler Thromb Vasc Biol, 2019, 39(2): e38-e81.
[4]	LEE M, CHENG C Y, WU Y L, et al. Association between intensity of low-density lipoprotein cholesterol reduction with statin-based therapies and secondary stroke prevention: a meta-analysis of randomized clinical trials[J]. JAMA Neurol, 2022, 79(4): 349.
[5]	DENG X J, WANG J H, YU S S, et al. Advances in the treatment of atherosclerosis with ligand-modified nanocarriers[J]. Exploration, 2024, 4(3): 20230090.
[6]	GAO C, HUANG Q X, LIU C H, et al. Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines[J]. Nat Commun, 2020, 11: 2622.
[7]	WANG Y-F, ZHANG C Q, YANG K N, et al. Transportation of AIE-visualized nanoliposomes is dominated by the protein corona[J]. Natl Sci Rev, 2021, 8(6): nwab068.
[8]	HO D, LYND T O, JUN C, et al. miR-146a encapsulated liposomes reduce vascular inflammatory responses through decrease of ICAM-1 expression, macrophage activation, and foam cell formation[J]. Nanoscale, 2023, 15(7): 3461-3474.
[9]	BENNE N, MARTINS CARDOSO R, BOYLE A L, et al. Complement receptor targeted liposomes encapsulating the liver X receptor agonist GW3965 accumulate in and stabilize atherosclerotic plaques[J]. Adv Healthc Mater, 2020, 9(10): 2000043.
[10]	LI Z X, ZHU H M, LIU H, et al. Evolocumab loaded bio-liposomes for efficient atherosclerosis therapy[J]. J Nanobiotechnol, 2023, 21(1): 158.
[11]	VAN DER VALK F M, VAN WIJK D F, LOBATTO M E, et al. Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration[J]. Nanomed Nanotechnol Biol Med, 2015, 11(5): 1039-1046.
[12]	ZHANG W L, HE H L, LIU J P, et al. Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone ⅡA discoidal and spherical biomimetic high density lipoproteins[J]. Biomaterials, 2013, 34(1): 306-319.
[13]	GUO Y H, YUAN W M, YU B L, et al. Synthetic high-density lipoprotein-mediated targeted delivery of liver X receptors agonist promotes atherosclerosis regression[J]. EBioMedicine, 2018, 28: 225-233.
[14]	ZHANG X Q, HUANG G L. Synthetic lipoprotein as nano-material vehicle in the targeted drug delivery[J]. Drug Deliv, 2017, 24(2): 16-21.
[15]	RONG T, WEI B, AO M Y, et al. Enhanced anti-atherosclerotic efficacy of pH-responsively releasable ganglioside GM3 delivered by reconstituted high-density lipoprotein[J]. Int J Mol Sci, 2021, 22(24): 13624.
[16]	ZHENG K H, KAISER Y, VAN OLDEN C C, et al. No benefit of HDL mimetic CER-001 on carotid atherosclerosis in patients with genetically determined very low HDL levels[J]. Atherosclerosis, 2020, 311: 13-19.
[17]	ITA K. Polyplexes for gene and nucleic acid delivery: progress and bottlenecks[J]. Eur J Pharm Sci, 2020, 150: 105358.
[18]	ZHANG L B, BEATTY A, LU L, et al. Microfluidic-assisted polymer-protein assembly to fabricate homogeneous functionalnanoparticles[J]. Mater Sci Eng C, 2020, 111: 110768.
[19]	WANG A Q, YUE K, ZHONG W S, et al. Targeted delivery of rapamycin and inhibition of platelet adhesion with multifunctional peptide nanoparticles for atherosclerosis treatment[J]. J Control Release, 2024, 376: 753-765.
[20]	WANG Y, LIU J, TONG C G, et al. Gene therapy by virus-like self-spooling toroidal DNA condensates for revascularization of hindlimb ischemia[J]. J Nanobiotechnol, 2024, 22(1): 413.
[21]	LI J J, WANG K X, PAN W, et al. Targeted imaging in atherosclerosis[J]. Anal Chem, 2022, 94(36): 12263-12273.
[22]	LIN Y Z, LIU J J, CHONG S Y, et al. Dual-function nanoscale coordination polymer nanoparticles for targeted diagnosis and therapeutic delivery in atherosclerosis[J]. Small, 2024, 20(47): 2401659.
[23]	JEON H, KIM J, LEE Y M, et al. Poly-paclitaxel/cyclodextrin-SPION nano-assembly for magnetically guided drug delivery system[J]. J Control Release, 2016, 231: 68-76.
[24]	MOU N L, DUAN X M, QU K, et al. Macrophage membrane spontaneously encapsulated cyclodextrin-based nanomedicines for improving lipid metabolism and inflammation in atherosclerosis[J]. ACS Appl Mater Interfaces, 2024, 16(37): 49660-49672.
[25]	WANG H H, ZHAO R Z, PENG L, et al. A dual-function CD47-targeting nano-drug delivery system used to regulate immune and anti-inflammatory activities in the treatment of atherosclerosis[J]. Adv Healthc Mater, 2024, 13(22): 2400752.
[26]	GUSTÀ M F, EDEL M J, SALAZAR V A, et al. Exploiting endocytosis for transfection of mRNA for cytoplasmatic delivery using cationic gold nanoparticles[J]. Front Immunol, 2023, 14: 1128582.
[27]	KIM H M, PARK J H, CHOI Y J, et al. Hyaluronic acid-coated gold nanoparticles as a controlled drug delivery system for poorly water-soluble drugs[J]. RSC Adv, 2023, 13(8): 5529-5537.
[28]	BOOMI P, GANESAN R, PRABU POORANI G, et al. Phyto-engineered gold nanoparticles (AuNPs) with potential antibacterial, antioxidant, and wound healing activities under in vitro and in vivo conditions[J]. Int J Nanomed, 2020, 15: 7553-7568.
[29]	LEE Y N, WU Y J, SU C H, et al. Fluorescent gold nanoclusters possess multiple actions against atherosclerosis[J]. Redox Biol, 2024, 78: 103427.
[30]	KHARLAMOV A N, TYURNINA A E, VESELOVA V S, et al. Silica-gold nanoparticles for atheroprotective management of plaques: results of the NANOM-FIM trial[J]. Nanoscale, 2015, 7(17): 8003-8015.
[31]	ZHANG H, LIU X L, FAN H M. Advances in magnetic nanoparticle-based magnetic resonance imaging contrast agents[J]. Nano Res, 2023, 16(11): 12531-12542.
[32]	PELLICO J, ELLIS C M, DAVIS J J. Nanoparticle-based paramagnetic contrast agents for magnetic resonance imaging[J]. Contrast Medium Mol Imag, 2019, 2019: 1845637.
[33]	TA H T, LI Z, HAGEMEYER C E, et al. Molecular imaging of activated platelets via antibody-targeted ultra-small iron oxide nanoparticles displaying unique dual MRI contrast[J]. Biomaterials, 2017, 134: 31-42.
[34]	ZOU L, ZHANG Y, CHERAGA N, et al. M2 macrophage membrane-camouflaged Fe₃O₄-Cy7 nanoparticles with reduced immunogenicity for targeted NIR/MR imaging of atherosclerosis[J]. Small, 2024, 20(8): 2304110.
[35]	LIN X F, DONG Q H, CHANG Y L, et al. Transition-metal-based nanozymes for biosensing and catalytic tumor therapy[J]. Anal Bioanal Chem, 2024, 416(27): 5933-5948.
[36]	WANG S, ZHANG J W, LI W, et al. Hyaluronic acid-guided assembly of ceria nanozymes as plaque-targeting ROS scavengers for anti-atherosclerotic therapy[J]. Carbohydr Polym, 2022, 296: 119940.
[37]	WANG L J, ZHANG X Q, ZHANG H R, et al. Novel metal-free nanozyme for targeted imaging and inhibition of atherosclerosis via macrophage autophagy activation to prevent vulnerable plaque formation and rupture[J]. ACS Appl Mater Interfaces, 2024, 16(39): 51944-51956.
[38]	HUANG X, ZHOU Y, et al. Selenium-doped copper formate nanozymes with antisenescence and oxidative stress reduction for atherosclerosis treatment[J]. Nano Lett, 2025, 25(7): 2662-2669.
[39]	WU Z Y, XU Z J, PU H J, et al. Degradable co-delivery nanoplatforms for inflammation-targeted therapy against atherosclerosis[J]. Appl Mater Today, 2021, 25: 101214.
[40]	WEI M, JIANG Q J, BIAN S, et al. Dual-mode-driven nanomotors targeting inflammatory macrophages for the MRI and synergistic treatment of atherosclerosis[J]. J Nanobiotechnol, 2025, 23(1): 54.
[41]	ZHANG J H, WANG Z W, LIAO Y H, et al. Black phosphorus nanoplatform coated with platelet membrane improves inhibition of atherosclerosis progression through macrophage targeting and efferocytosis[J]. Acta Biomater, 2025, 192: 377-393.
[42]	HE Z S, CHEN W, HU K, et al. Resolvin D1 delivery to lesional macrophages using antioxidative black phosphorus nanosheets for atherosclerosis treatment[J]. Nat Nanotechnol, 2024, 19(9): 1386-1398.
[43]	CHEN L, HONG W Q, REN W Y, et al. Recent progress in targeted delivery vectors based on biomimetic nanoparticles[J]. Sig Transduct Target Ther, 2021, 6: 225.
[44]	YAO Y Y, CHEN H T, BARKAT A, et al. A zombie macrophage-based "Trojan horse" enhances the effect of efferocytosis through immune regulation for atherosclerosis treatment[J]. Adv Funct Materials, 2024, 34(27): 2315034.
[45]	HUANG R Z, ZHANG L J, LI X S, et al. Anti-CXCR2 antibody-coated nanoparticles with an erythrocyte-platelet hybrid membrane layer for atherosclerosis therapy[J]. J Control Release, 2023, 356: 610-622.
[46]	LI L H, LU Y, JIANG C Y, et al. Actively targeted deep tissue imaging and photothermal-chemo therapy of breast cancer by antibody-functionalized drug-loaded X-ray-responsive bismuth Sulfide@Mesoporous silica core-shell nanoparticles[J]. Adv Funct Materials, 2018, 28(5): 1704623.
[47]	LOHCHAROENKAL W, WANG L Y, CHEN Y C, et al. Protein nanoparticles as drug delivery carriers for cancer therapy[J]. BioMed Res Int, 2014, 2014: 180549.
[48]	KONDYLIS P, SCHLICKSUP C J, ZLOTNICK A, et al. Analytical techniques to characterize the structure, properties, and assembly of virus capsids[J]. Anal Chem, 2019, 91(1): 622-636.
[49]	XU R T, OUYANG L X, CHEN H Y, et al. Recent advances in biomolecular detection based on aptamers and nanoparticles[J]. Biosensors, 2023, 13(4): 474.
[50]	HE F, WEN N C, XIAO D P, et al. Aptamer-based targeted drug delivery systems: current potential and challenges[J]. Curr Med Chem, 2020, 27(13): 2189-2219.
[51]	WANG Y H, HUANG G J, HOU Q, et al. Cell surface-nanoengineering for cancer targeting immunoregulation and precise immunotherapy[J]. WIREs Nanomed Nanobiotechnol, 2023, 15(4): e1875.
[52]	SHI Y, DONG M, WU Y, et al. An elastase-inhibiting, plaque-targeting and neutrophil-hitchhiking liposome against atherosclerosis[J]. Acta Biomater, 2024, 173: 470-481.
[53]	YE Y C, HUANG L, WANG K J, et al. Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia[J]. J Tissue Eng, 2025, 16: 20417314251315959.
[54]	CHEN S Y, SU Y, ZHANG M J, et al. Insights into the toxicological effects of nanomaterials on atherosclerosis: mechanisms involved and influence factors[J]. J Nanobiotechnol, 2023, 21(1): 140.
[55]	IAFISCO M, ALOGNA A, MIRAGOLI M, et al. Cardiovascular nanomedicine: the route ahead[J]. Nanomedicine, 2019, 14(18): 2391-2394.
[56]	ZHANG Z, DALAN R, HU Z Y, et al. Reactive oxygen species scavenging nanomedicine for the treatment of ischemic heart disease[J]. Adv Mater, 2022, 34(35): 2202169.

Type	Advantage	Limitation	Research phase
Lipid-based NPs	High drug loading capacity, gene delivery capability, natural targeting, and high biocompatibility	Low stability, and shortened in vivo circulation time	Predominantly preclinical investigations, with selective progression to clinical trials
Polymer NPs	Tunable structural properties, stimuli-responsive behavior, and broad-spectrum drug compatibility	Multi-step synthesis process, limited in vivo stability, and potential toxicity risks	Comprehensive preclinical investigation with selective, clinical translation-oriented studies
Inorganic NPs	Precise controllability, theranostic integration, and high stability	Potential toxicity risks, incompletely characterized metabolic pathways, and undetermined long-term safety profiles	Predominantly preclinical investigation, with a limited subset progressing to clinical trials
Biomimetic NPs	High biocompatibility, prolonged circulation time, and homology-directed targeting	Complex multi-step synthesis, restricted membrane availability, and challenges in standardization	Active preclinical research, remaining largely in the preclinical phase without clinical progression

Type	Advantage	Limitation	Research phase
Lipid-based NPs	High drug loading capacity, gene delivery capability, natural targeting, and high biocompatibility	Low stability, and shortened in vivo circulation time	Predominantly preclinical investigations, with selective progression to clinical trials
Polymer NPs	Tunable structural properties, stimuli-responsive behavior, and broad-spectrum drug compatibility	Multi-step synthesis process, limited in vivo stability, and potential toxicity risks	Comprehensive preclinical investigation with selective, clinical translation-oriented studies
Inorganic NPs	Precise controllability, theranostic integration, and high stability	Potential toxicity risks, incompletely characterized metabolic pathways, and undetermined long-term safety profiles	Predominantly preclinical investigation, with a limited subset progressing to clinical trials
Biomimetic NPs	High biocompatibility, prolonged circulation time, and homology-directed targeting	Complex multi-step synthesis, restricted membrane availability, and challenges in standardization	Active preclinical research, remaining largely in the preclinical phase without clinical progression