In the last several decades, cardiovascular diseases (CVDs) have emerged as a major hazard to human life and health. Conventional formulations for the treatment of CVD are available, but they are far from ideal because of poor water solubility, limited biological activity, non-targeting, and drug resistance. With the advancement of nanotechnology, a novel drug delivery approach for the treatment of CVDs has emerged: nano-drug delivery systems (NDDSs). NDDSs have shown significant advantages in tackling the difficulties listed above. Cytotoxicity is a difficulty with the use of non-destructive DNA sequences. NDDS categories and targeted tactics were outlined, as well as current research advancements in the diagnosis and treatment of CVDs. It’s possible that gene therapy might be included into nano-carriers in the delivery of cardiovascular medications in the future. In addition, the evaluation addressed the drug’s safety.

1. Gaurav C, Saurav B, Goutam R, et al. Nano-systems for advanced therapeutics and diagnosis of atherosclerosis. Current Pharmaceutical Design 2015; 21(30): 4498–4508. doi: 10.2174/1381612821666150917094215.

2. Quan X, Rang L, Yin X, et al. Synthesis of PEGylated hyaluronic acid for loading dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt) in nanoparticles for cancer treatment. Chinese Chemical Letters 2015; 26(6): 695–699. doi: 10.1016/j.cclet.2015.04.024.

3. Landesman-Milo D, Goldsmith M, Leviatan BS, et al. Hyaluronan grafted lipid-based nanoparticles as RNAi carriers for cancer cells. Cancer Letters 2013; 334(2): 221–227. doi: 10.1016/j.canlet.2012.08.024.

4. Chandrasekaran S, King MR. Microenvironment of tumor-draining lymph nodes: Opportunities for liposome-based targeted therapy. International Journal of Molecular Sciences 2014; 15(11): 20209–20239. doi: 10.3390/ijms151120209.

5. Fan Y, Chen C, Huang Y, et al. Study of the pH-sensitive mechanism of tumor-targeting liposomes. Colloids and Surfaces B: Biointerfaces 2017; 151: 19–25. doi: 10.1016/j.colsurfb.2016.11.042.

6. Li Z, Ding J, Xiao C, et al. Glucose-sensitive polypeptide micelles for self-regulated insulin release at physiological pH. Journal of Materials Chemistry 2012; 22(24): 12319–12328. doi: 10.1039/c2jm31040f.

7. Afsharzadeh M, Hashemi M, Mokhtarzadeh A, et al. Recent advances in co-delivery systems based on polymeric nanoparticle for cancer treatment. Artificial Cells, Nanomedicine, and Biotechnology 2018; 46(6): 1095–1110. doi: 10.1080/21691401.2017.1376675.

8. Wang W, Ding J, Xiao C, et al. Synthesis of amphiphilic alternating polyesters with oligo(ethylene glycol) side chains and potential use for sustained release drug delivery. Biomacromolecules 2011; 12(7): 2466–2474. doi: 10.1021/bm200668n.

9. Ping S, Wei H, Lin K, et al. siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis. International Journal of Nanomedicine 2017; 12: 3221–3234. doi: 10.2147/IJN.S129436.

10. Kesharwani P, Gajbhiye V, Jain NK. A review of nanocarriers for the delivery of small interfering RNA. Biomaterials 2012; 33(29): 7138–7150. doi: 10.1016/j.biomaterials.2012.06.068.

11. Baeza A, Ruiz-Molina D, Vallet-Regi M. Recent advances in porous nanoparticles for drug delivery in antitumoral applications: inorganic nanoparticles and nanoscale metal-organic frameworks. Expert Opinion on Drug Delivery 2017; 14(6): 783–796. doi: 10.1080/17425247.2016.1229298

12. Liang JJ, Zhou YY, Wu J, et al. Gold nanoparticle-based drug delivery platform for antineoplastic chemotherapy. Current Drug Metabolism 2014; 15(6): 620–631. doi: 10.2174/1389200215666140605131427.

13. Khafaji M, Zamani M, Golizadeh M, et al. Inorganic nanomaterials for chemo/photothermal therapy: A promising horizon on effective cancer treatment. Biophysical Reviews 2019; 11(3): 335–352. doi: 10.1007/s12551-019-00532-3

14. Perioli L, Pagano C, Ceccarini MR. Current highlights about the safety of inorganic nanomaterials in healthcare. Current Medicinal Chemistry 2019; 26(12): 2147–2165. doi: 10.2174/0929867325666180723121804.

15. Zhang Z, Runa A, Wu J, et al. Bioresponsive nanogated ensemble based on structure-switchable aptamer directed assembly and disassembly of gold nanoparticles from mesoporous silica supports. Chinese Chemical Letters 2019; 30(3): 267–270. doi: 10.1016/j.cclet.2018.10.019.

16. Holback H, Yeo Y. Intratumoral drug delivery with nanoparticulate carriers. Pharmaceutical Research 2011; 28(8): 1819–1830. doi: 10.1007/s11095-010-0360-y.

17. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Advanced Drug Delivery Reviews 2013; 65(1): 71–79. doi: 10.1016/j.addr.2012.10.002.

18. Flogel U, Ding Z, Hardung H, et al. In vivo monitoring of inflammation after cardiac and cerebral ischemia by fluorine magnetic resonance imaging. Circulation 2008; 118(2): 140–148. doi: 10.1161/CIRCULATIONAHA.107.737890.

19. Hemmati K, Ghaemy M. Synthesis of new thermo/pH sensitive drug delivery systems based on tragacanth gum polysaccharide. International Journal of Biological Macromolecules 2016; 87: 415–425. doi: 10.1016/j.ijbiomac.2016.03.005.

20. Korin N, Kanapathipillai M, Matthews BD, et al. Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science 2012; 337(6095): 738–742. doi: 10.1126/science.1217815.

21. Tan J, Thomas A, Liu Y. Influence of red blood cells on nanoparticle targeted delivery in microcirculation. Soft Matter 2011; 8: 1934–1946. doi: 10.1039/C2SM06391C.

22. Alam SR, Stirrat C, Richards J, et al. Vascular and plaque imaging with ultrasmall superparamagnetic particles of iron oxide. Journal of Cardiovascular Magnetic Resonance 2015; 17: 83. doi: 10.1186/s12968-015-0183-4.

23. Freund B, Shapiro B. Transport of particles by magnetic forces and cellular blood flow in a model microvessel. Physics of Fluids 2012; 24(5). doi: 10.1063/1.4718752.

24. Matoba T, Egashira K. Nanoparticle-mediated drug delivery system for cardiovascular disease. International Heart Journal 2014; 55: 281–286. doi: 10.1536/ihj.14-150.

25. Glass CK, Witztum JL. Atherosclerosis. the road ahead. Cell 2001; 104(4): 503–516. doi: 10.1016/s0092-8674(01)00238-0.

26. Hood ED, Greineder CF, Shuvaeva T, et al. Vascular targeting of radiolabeled liposomes with bio-orthogonally conjugated ligands: Single chain fragments provide higher specificity than antibodies. Bioconjugate Chemistry 29(11): 3626–3637. doi: 10.1021/acs.bioconjchem.8b00564.

27. Paulis LE, Jacobs I, van den Akker NM, et al. Targeting of ICAM-1 on vascular endothelium under static and shear stress conditions using a liposomal Gd-based MRI contrast agent. Journal of Nanobiotechnology 2012; 10: 25. doi: 10.1186/1477-3155-10-25.

28. Ma S, Tian XY, Zhang Y, et al. E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis. Scientific Reports 2016; 6: 22910. doi: 10.1038/srep22910.

29. Flaht-Zabost A, Gula G, Ciszek B, et al. Cardiac mouse lymphatics: Developmental and anatomical update. Anatomical Record 2014; 297(6): 1115–1130. doi: 10.1002/ar.22912.

30. Dvir T, Bauer M, Schroeder A, et al. Nanoparticles targeting the infarcted heart. Nano Letters 2011; 11(10): 4411–4414.doi: 10.1021/nl2025882.

31. Lee GY, Kim JH, Choi KY, et al. Hyaluronic acid nanoparticles for active targeting atherosclerosis. Biomaterials 2015; 53: 341–348. doi: 10.1016/j.biomaterials.2015.02.089.

32. Kamaly N, Fredman G, Fojas JJ, et al. Targeted interleukin-10 nanotherapeutics developed with a microfluidic chip enhance resolution of inflammation in advanced atherosclerosis. ACS Nano 2016; 10(5): 5280–5292. doi: 10.1021/acsnano.6b01114.

33. Anselmo AC, Modery-Pawlowski CL, Menegatti S, et al. Platelet-like nanoparticles: Mimicking shape, flexibility, and surface biology of platelets to target vascular injuries. ACS Nano 2014; 8(11): 11243–11253. doi: 10.1021/nn503732m.

34. Charoenphol P, Mocherla S, Bouis D, et al. Targeting therapeutics to the vascular wall in atherosclerosis—Carrier size matters. Atherosclerosis 2011; 217(2): 364–370. doi: 10.1016/j.atherosclerosis.2011.04.016.

35. Corot C, Robert P, Idee JM, et al. Recent advances in iron oxide nanocrystal technology for medical imaging. Advanced Drug Delivery Reviews 2006; 58(14): 1471–1504. doi: 10.1016/j.addr.2006.09.013.

36. Yoo SP, Pineda F, Barrett JC, et al. Gadolinium-functionalized peptide amphiphile micelles for multimodal imaging of atherosclerotic lesions. ACS Omega 2016; 1(5): 996–1003. doi: 10.1021/acsomega.6b00210.

37. Winter PM, Caruthers SD, Zhang H, et al. Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis. JACC: Cardiovascular Imaging 2008; 1(5): 624–634. doi: 10.1016/j.jcmg.2008.06.003.

38. Mottu F, Rüfenacht DA, Laurent A, et al. Iodine-containing cellulose mixed esters as radiopaque polymers for direct embolization of cerebral aneurysms and arteriovenous malformations. Biomaterials 2002; 23(1): 121–131. doi: 10.1016/s0142-9612(01)00087-4.

39. Alie N, Eldib M, Fayad ZA, et al. Inflammation, atherosclerosis, and coronary artery disease: PET/CT for the evaluation of atherosclerosis and inflammation. Clinical Medicine Insights: Cardiology 2015; 8(Suppl 3): 13–21. doi: 10.4137/CMC.S17063.

40. Chhour P, Naha PC, O’Neill SM, et al. Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography. Biomaterials 2016; 87: 93–103. doi: 10.1016/j.biomaterials.2016.02.009.

41. Wang Y, Chen J, Yang B, et al. In vivo MR and fluorescence dual-modality imaging of atherosclerosis characteristics in mice using profilin-1 targeted magnetic nanoparticles. Theranostics 2016; 6(2): 272–286. doi: 10.7150/thno.13350.

42. Marsh JN, Senpan A, Hu G, et al. Fibrin-targeted perfluorocarbon nanoparticles for targeted thrombolysis. Nanomedicine 2007; 2(4): 533–543. doi: 10.2217/17435889.2.4.533.

43. Yang X, Hong H, Grailer JJ, et al. cRGD-functionalized, DOX-conjugated, and 64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging. Biomaterials 2011; 32(17): 4151–4160. doi: 10.1016/j.biomaterials.2011.02.006.

44. Chen J, Sun Y, Chen Q, et al. Multifunctional gold nanocomposites designed for targeted CT/MR/optical trimodal imaging of human non-small cell lung cancer cells. Nanoscale 2016; 8(28): 13568–13573. doi: 10.1039/c6nr03143a.

45. Bejarano J, Navarro-Marquez M, Morales-Zavala F, et al. Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction: Evolution toward prospective theranostic approaches. Theranostics 2018; 8(17): 4710–4732. doi: 10.7150/thno.26284.

46. Sharma M, Sharma R, Jain DK. Nanotechnology based approaches for enhancing oral bioavailability of poorly water soluble antihypertensive drugs. Scientifica 2016; 2016: 8525679. doi: 10.1155/2016/8525679.

47. Alam T, Khan S, Gaba B, et al. Nanocarriers as treatment modalities for hypertension. Drug Delivery 2017; 24(1): 358–369. doi: 10.1080/10717544.2016.12 55999.

48. Ghasemian E, Motaghian P, Vatanara A. D-optimal design for preparation and optimization of fast dissolving Bosentan nanosuspension. Advanced Pharmaceutical Bulletin 2016; 6(2): 211. doi: 10.15171/apb.2016.029.

49. Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: A neglected therapeutic target. Journal of Clinical Investigation 2013; 123(1): 92–100. doi: 10.1172/JCI62874.

50. Barbieri LR, Lourenço-Filho DD, Tavares ER, et al. Influence of drugs carried in lipid nanoparticles in coronary disease of rabbit transplanted heart. Annals of Thoracic Surgery 2017; 104(2): 577–583. doi: 10.1016/j.athoracsur.2016.12.044.

51. Zhou X, Luo YC, Ji WJ, et al. Modulation of mononuclear phagocyte inflammatory response by liposome-encapsulated voltage gated sodium channel inhibitor ameliorates myocardial ischemia/reperfusion injury in rats. PLoS ONE 2013; 8(9): e0074390. doi: 10.1371/journal.pone.00 74390.

52. Wu T, Ding M, Shi C, et al. Resorbable polymer electrospun nanofibers: History, shapes and application for tissue engineering. Chinese Chemical Letters 2020; 31(3): 617–625. doi: 10.1016/j.cclet.2019.07.033.

53. Braukmann F, Jordan D, Miska E. Artificial and natural RNA interactions between bacteria and C. elegans. RNA Biology 2017; 14(4): 415–420. doi: 10.1080/15476286.2017.1297912.

54. Katyayani T, Samaresh S, Sushil K, et al. siRNA delivery strategies: A comprehensive review of recent developments. Nanomaterials 2017; 7(4): 77. doi: 10.3390/nano7040077.

55. Cotten M, Wagner E, Zatloukal K, et al. High-efficiency receptor-mediated delivery of small and large (48 kilobase gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles. Proceedings of the National Academy of Sciences of the United States of America 1992; 89(13): 6094–6098. doi: 10.1073/pnas.89.13.6094.

56. Zimmermann TS, Lee ACH, Akinc A, et al. RNAi-mediated gene silencing in non-human primates. Nature 2006; 441(7089): 111–114. doi: 10.1038/nature04688.

57. Somasuntharam I, Boopathy AV, Khan RS, et al. Delivery of Nox2-NADPH oxidase siRNA with polyketal nanoparticles for improving cardiac function following myocardial infarction. Biomaterials 2013; 34(31): 7790–7798. doi: 10.1016/j.biomaterials.2013.06.051.

58. Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: A randomised, single-blind, placebo-controlled, phase 1 trial. Lancet 2014; 383(9911): 60–68. doi: 10.1016/S0140-6736(13)61914-5.

59. Gatoo MA, Naseem S, Arfat MY, et al. Physicochemical properties of nanomaterials: Implication in associated toxic manifestations. BioMed Research International 2014; 2014: 498420. doi: 10.1155/2014/498420.

60. Donnini D, Perrella G, Stel G, et al. A new model of human aortic endothelial cells in vitro. Biochimie 2000; 82(12): 1107–1114. doi: 10.1016/s0300-9084(00)01195-0.

61. Suwa T, Hogg JC, Quinlan KB, et al. Particulate air pollution induces progression of atherosclerosis. Journal of the American College of Cardiology 2002; 39(6): 935–942. doi: 10.1016/s0735-1097(02)01715-1.

62. Chen M, Von MA. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Experimental Cell Research 2005; 305(1): 51–62. doi: 10.1016/j.yexcr.2004.12.021.

63. Han W, Li H, Yu X, et al. In vivo toxicity evaluation of a nano-drug delivery system using a Caenorhabditis elegans model system. Chemical Research in Chinese Universities 2021; 38: 1018–1024.

64. Tedla N, Jose R, Vicky M, et al. Synthesis, Pharmacokinetics, and toxicity of nano-drug carriers. In: Nanocarriers: Drug delivery system. Singapore: Springer; 2021. p. 63–106.

65. Patnaik S, Gorain B, Padhi S, et al. Recent update of toxicity aspects of nanoparticulate systems for drug delivery. European Journal of Pharmaceutics and Biopharmaceutics 2021; 161: 100–119.