Nanomedicine is an application of nanotechnology that provides solutions to unmet medical challenges. The unique features of nanoparticles, such as their small size, modifiable components, and diverse functionality, make them attractive and suitable materials for novel diagnostic, therapeutic, or theranostic applications. Cardiovascular diseases (CVDs) are the major cause of noncommunicable illness in both developing and developed countries. Nanomedicine offers novel theranostic options for the treatment of CVDs.
Recent Advances:
Many innovative nanoparticles to target reactive oxygen species (ROS) have been developed. In this article, we review the characteristics of nanoparticles that are responsive to ROS, their limitations, and their potential clinical uses. Significant advances made in diagnosis of atherosclerosis and treatment of acute coronary syndrome using nanoparticles are discussed.
Critical Issues:
Although there is a tremendous potential for the nanoparticle applications in medicine, their safety should be considered while using in humans. We discuss the challenges that may be encountered with some of the innovative nanoparticles used in CVDs.
Future Directions:
The unique properties of nanoparticles offer novel diagnostic tool and potential therapeutic strategies. However, nanomedicine is still in its infancy, and further in-depth studies are needed before wide clinical application is achieved.
Get full access to this article
View all access options for this article.
References
1.
AgyareE and KandimallaK. Delivery of polymeric nanoparticles to target vascular diseases. J Biomol Res Ther, 3: S1–001, 2014.
2.
AhamedM, AlsalhiMS, and SiddiquiMK. Silver nanoparticle applications and human health. Clin Chim Acta, 411: 1841–1848, 2010.
3.
AlibakhshiA, Abarghooi KahakiF, AhangarzadehS, YaghoobiH, YarianF, ArezumandR, RanjbariJ, MokhtarzadehA, and de la GuardiaM. Targeted cancer therapy through antibody fragments-decorated nanomedicines. J Control Release, 268: 323–334, 2017.
4.
AndiaME, SahaP, JenkinsJ, ModaraiB, WiethoffAJ, PhinikaridouA, GroverSP, PatelAS, SchaeffterT, SmithA, and BotnarRM. Fibrin-targeted magnetic resonance imaging allows in vivo quantification of thrombus fibrin content and identifies thrombi amenable for thrombolysis. Arterioscler Thromb Vasc Biol, 34: 1193–1198, 2014.
5.
AnselmoAC and MitragotriS. A review of clinical translation of inorganic nanoparticles. AAPS J, 17: 1041–1054, 2015.
6.
BenjaminEJ, BlahaMJ, ChiuveSE, CushmanM, DasSR, DeoR, de FerrantiSD, FloydJ, FornageM, GillespieC, IsasiCR, JimenezMC, JordanLC, JuddSE, LacklandD, LichtmanJH, LisabethL, LiuS, LongeneckerCT, MackeyRH, MatsushitaK, MozaffarianD, MussolinoME, NasirK, NeumarRW, PalaniappanL, PandeyDK, ThiagarajanRR, ReevesMJ, RitcheyM, RodriguezCJ, RothGA, RosamondWD, SassonC, TowfighiA, TsaoCW, TurnerMB, ViraniSS, VoeksJH, WilleyJZ, WilkinsJT, WuJH, AlgerHM, WongSS, and MuntnerP. Heart disease and stroke statistics-2017 update: a Report From the American Heart Association. Circulation, 135: e146–e603, 2017.
7.
BiF, ZhangJ, SuY, TangYC, and LiuJN. Chemical conjugation of urokinase to magnetic nanoparticles for targeted thrombolysis. Biomaterials, 30: 5125–5130, 2009.
8.
BostanHB, RezaeeR, ValokalaMG, TsarouhasK, GolokhvastK, TsatsakisAM, and KarimiG. Cardiotoxicity of nano-particles. Life Sci, 165: 91–99, 2016.
9.
BraunersreutherV, MontecuccoF, AsrihM, PelliG, GalanK, FriasM, BurgerF, QuindereAL, MontessuitC, KrauseKH, MachF, and JaquetV. Role of NADPH oxidase isoforms NOX1, NOX2 and NOX4 in myocardial ischemia/reperfusion injury. J Mol Cell Cardiol, 64: 99–107, 2013.
10.
CabralH and KataokaK. Progress of drug-loaded polymeric micelles into clinical studies. J Control Release, 190: 465–476, 2014.
11.
ChangEH, HarfordJB, EatonMA, BoisseauPM, DubeA, HayeshiR, SwaiH, and LeeDS. Nanomedicine: past, present and future—a global perspective. Biochem Biophys Res Commun, 468: 511–517, 2015.
12.
ChauhanG, ChopraV, TyagiA, RathG, SharmaRK, and GoyalAK. “Gold nanoparticles composite-folic acid conjugated graphene oxide nanohybrids” for targeted chemo-thermal cancer ablation: in vitro screening and in vivo studies. Eur J Pharm Sci, 96: 351–361, 2017.
ChenHH, FengY, ZhangM, ChaoW, JosephsonL, ShawSY, and SosnovikDE. Protective effect of the apoptosis-sensing nanoparticle AnxCLIO-Cy5.5. Nanomedicine, 8: 291–298, 2012.
15.
ChenJP, YangPC, MaYH, TuSJ, and LuYJ. Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle. Int J Nanomedicine, 7: 5137–5149, 2012.
16.
ChengCJ, TietjenGT, Saucier-SawyerJK, and SaltzmanWM. A holistic approach to targeting disease with polymeric nanoparticles. Nat Rev Drug Discov, 14: 239–247, 2015.
17.
CisternaBA, KamalyN, ChoiWI, TavakkoliA, FarokhzadOC, and VilosC. Targeted nanoparticles for colorectal cancer. Nanomedicine (Lond), 11: 2443–2456, 2016.
18.
CostanzoL.Cardiovascular physiology. In: Physiology, 5th ed., edited by CostanzoL.Philadelphia, PA: Lippincott Williams & Wilkins, 2011, pp. 64–99.
19.
DaiQ, Bertleff-ZieschangN, BraungerJA, BjornmalmM, Cortez-JugoC, and CarusoF. Particle targeting in complex biological media. Adv Healthc Mater, 7: 1700575, 2018.
20.
DanhierF, FeronO, and PreatV. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release, 148: 135–146, 2010.
21.
DaviG and PatronoC. Platelet activation and atherothrombosis. N Engl J Med, 357: 2482–2494, 2007.
22.
DimN, PerepelyukM, GomesO, ThangavelC, LiuY, DenR, LakshmikuttyammaA, and ShoyeleSA. Novel targeted siRNA-loaded hybrid nanoparticles: preparation, characterization and in vitro evaluation. J Nanobiotechnology, 13: 61, 2015.
23.
DonCW and MurryCE. Improving survival and efficacy of pluripotent stem cell-derived cardiac grafts. J Cell Mol Med, 17: 1355–1362, 2013.
24.
EnglandCG, ImHJ, FengL, ChenF, GravesSA, HernandezR, OrbayH, XuC, ChoSY, NicklesRJ, LiuZ, LeeDS, and CaiW. Re-assessing the enhanced permeability and retention effect in peripheral arterial disease using radiolabeled long circulating nanoparticles. Biomaterials, 100: 101–109, 2016.
EvansCW, IyerKS, and HoolLC. The potential for nanotechnology to improve delivery of therapy to the acute ischemic heart. Nanomedicine (Lond), 11: 817–832, 2016.
27.
FiggeL, ApplerF, ChenHH, SosnovikDE, SchnorrJ, SeitzO, TaupitzM, HammB, and SchellenbergerE. Direct coupling of annexin A5 to VSOP yields small, protein-covered nanoprobes for MR imaging of apoptosis. Contrast Media Mol Imaging, 9: 291–299, 2014.
28.
GaharwarAK, PeppasNA, and KhademhosseiniA. Nanocomposite hydrogels for biomedical applications. Biotechnol Bioeng, 111: 441–453, 2014.
29.
GalagudzaM, KorolevD, PostnovV, NaumishevaE, GrigorovaY, UskovI, and ShlyakhtoE. Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles. Int J Nanomedicine, 7: 1671–1678, 2012.
30.
GannonCJ, PatraCR, BhattacharyaR, MukherjeeP, and CurleySA. Intracellular gold nanoparticles enhance non-invasive radiofrequency thermal destruction of human gastrointestinal cancer cells. J Nanobiotechnology, 6: 2, 2008.
GeelenT, PaulisLE, CoolenBF, NicolayK, and StrijkersGJ. Passive targeting of lipid-based nanoparticles to mouse cardiac ischemia-reperfusion injury. Contrast Media Mol Imaging, 8: 117–126, 2013.
33.
GrayWD, CheP, BrownM, NingX, MurthyN, and DavisME. N-acetylglucosamine conjugated to nanoparticles enhances myocyte uptake and improves delivery of a small molecule p38 inhibitor for post-infarct healing. J Cardiovasc Transl Res, 4: 631–643, 2011.
34.
GrottkauBE, CaiX, WangJ, YangX, and LinY. Polymeric nanoparticles for a drug delivery system. Curr Drug Metab, 14: 840–846, 2013.
35.
Group TNt-PSS. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group. Stroke, 28: 2109–2118, 1997.
36.
GuoY, ChenW, WangW, ShenJ, GuoR, GongF, LinS, ChengD, ChenG, and ShuaiX. Simultaneous diagnosis and gene therapy of immuno-rejection in rat allogeneic heart transplantation model using a T-cell-targeted theranostic nanosystem. ACS Nano, 6: 10646–10657, 2012.
37.
HanHS, LeeJ, KimHR, ChaeSY, KimM, SaravanakumarG, YoonHY, YouDG, KoH, KimK, KwonIC, ParkJC, and ParkJH. Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin: mineralization and its effect on tumor targetability in vivo. J Control Release, 168: 105–114, 2013.
38.
HausenloyDJ and YellonDM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest, 123: 92–100, 2013.
39.
HayashiK, NakamuraM, MikiH, OzakiS, AbeM, MatsumotoT, and IshimuraK. Gold nanoparticle cluster-plasmon-enhanced fluorescent silica core-shell nanoparticles for X-ray computed tomography-fluorescence dual-mode imaging of tumors. Chem Commun (Camb), 49: 5334–5336, 2013.
40.
HemburyM, ChiappiniC, BertazzoS, KalberTL, DriskoGL, OgunladeO, Walker-SamuelS, KrishnaKS, JumeauxC, BeardP, KumarCS, PorterAE, LythgoeMF, BoissiereC, SanchezC, and StevensMM. Gold-silica quantum rattles for multimodal imaging and therapy. Proc Natl Acad Sci U S A, 112: 1959–1964, 2015.
41.
HirsjarviS, PassiraniC, and BenoitJP. Passive and active tumour targeting with nanocarriers. Curr Drug Discov Technol, 8: 188–196, 2011.
42.
HoYT, PoinardB, and KahJC. Nanoparticle drug delivery systems and their use in cardiac tissue therapy. Nanomedicine (Lond), 11: 693–714, 2016.
43.
Hofmann-AmtenbrinkM, GraingerDW, and HofmannH. Nanoparticles in medicine: current challenges facing inorganic nanoparticle toxicity assessments and standardizations. Nanomedicine, 11: 1689–1694, 2015.
44.
HuJ, XieL, ZhaoW, SunM, LiuX, and GaoW. Design of tumor-homing and pH-responsive polypeptide-doxorubicin nanoparticles with enhanced anticancer efficacy and reduced side effects. Chem Commun (Camb), 51: 11405–11408, 2015.
45.
IbanezB, HeuschG, OvizeM, and Van de WerfF. Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol, 65: 1454–1471, 2015.
46.
ImHJ, EnglandCG, FengL, GravesSA, HernandezR, NicklesRJ, LiuZ, LeeDS, ChoSY, and CaiW. Accelerated blood clearance phenomenon reduces the passive targeting of PEGylated nanoparticles in peripheral arterial disease. ACS Appl Mater Interfaces, 8: 17955–17963, 2016.
47.
JainAK, MehraNK, and SwarnakarNK. Role of antioxidants for the treatment of cardiovascular diseases: challenges and opportunities. Curr Pharm Des, 21: 4441–4455, 2015.
48.
JinS, WangY, ZhuH, WangY, ZhaoS, ZhaoM, LiuJ, WuJ, GaoW, and PengS. Nanosized aspirin-Arg-Gly-Asp-Val: delivery of aspirin to thrombus by the target carrier Arg-Gly-Asp-Val tetrapeptide. ACS Nano, 7: 7664–7673, 2013.
49.
Joshi-BarrS, de Gracia LuxC, MahmoudE, and AlmutairiA. Exploiting oxidative microenvironments in the body as triggers for drug delivery systems. Antioxid Redox Signal, 21: 730–754, 2014.
50.
KamataH, LiX, ChungUI, and SakaiT. Design of hydrogels for biomedical applications. Adv Healthc Mater, 4: 2360–2374, 2015.
51.
KangC, GwonS, SongC, KangPM, ParkSC, JeonJ, HwangDW, and LeeD. Fibrin-targeted and H2O2-responsive nanoparticles as a theranostics for thrombosed vessels. ACS Nano, 11: 6194–6203, 2017.
52.
KaragkiozakiV, LogothetidisS, and PappaAM. Nanomedicine for atherosclerosis: molecular imaging and treatment. J Biomed Nanotechnol, 11: 191–210, 2015.
53.
KarakasM and KoenigW. Myeloperoxidase production by macrophage and risk of atherosclerosis. Curr Atheroscler Rep, 14: 277–283, 2012.
54.
KimT and HyeonT. Applications of inorganic nanoparticles as therapeutic agents. Nanotechnology, 25: 012001, 2014.
55.
KimuraW, MuralidharS, CansecoDC, PuenteB, ZhangCC, XiaoF, AbderrahmanYH, and SadekHA. Redox signaling in cardiac renewal. Antioxid Redox Signal, 21: 1660–1673, 2014.
56.
KlonerRA, BrownDA, CseteM, DaiW, DowneyJM, GottliebRA, HaleSL, and ShiJ. New and revisited approaches to preserving the reperfused myocardium. Nat Rev Cardiol, 14: 679–693, 2017.
57.
KornfeldOS, HwangS, DisatnikMH, ChenCH, QvitN, and Mochly-RosenD. Mitochondrial reactive oxygen species at the heart of the matter: new therapeutic approaches for cardiovascular diseases. Circ Res, 116: 1783–1799, 2015.
58.
KumarS, AswalVK, and CallowP. pH-dependent interaction and resultant structures of silica nanoparticles and lysozyme protein. Langmuir, 30: 1588–1598, 2014.
LeeD, BaeS, KeQ, LeeJ, SongB, KarumanchiSA, KhangG, ChoiHS, and KangPM. Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and therapy of ischemia-reperfusion injury. J Control Release, 172: 1102–1110, 2013.
63.
LiY, GaoGH, and LeeDS. Stimulus-sensitive polymeric nanoparticles and their applications as drug and gene carriers. Adv Healthc Mater, 2: 388–417, 2013.
64.
LinCW, TsengSJ, KempsonIM, YangSC, HongTM, and YangPC. Extracellular delivery of modified oligonucleotide and superparamagnetic iron oxide nanoparticles from a degradable hydrogel triggered by tumor acidosis. Biomaterials, 34: 4387–4393, 2013.
65.
LiuY, QiaoL, ZhangS, WanG, ChenB, ZhouP, ZhangN, and WangY. Dual pH-responsive multifunctional nanoparticles for targeted treatment of breast cancer by combining immunotherapy and chemotherapy. Acta Biomater S1742-7061(17)30696–30697, 2017.
66.
LuoE, SongG, LiY, ShiP, HuJ, and LinY. The toxicity and pharmacokinetics of carbon nanotubes as an effective drug carrier. Curr Drug Metab, 14: 879–890, 2013.
67.
LuoGF, ChenWH, LiuY, LeiQ, ZhuoRX, and ZhangXZ. Multifunctional enveloped mesoporous silica nanoparticles for subcellular co-delivery of drug and therapeutic peptide. Sci Rep, 4: 6064, 2014.
68.
MadamanchiNR and RungeMS. Redox signaling in cardiovascular health and disease. Free Radic Biol Med, 61: 473–501, 2013.
69.
MaheshwariR, TekadeM, SharmaPA, and TekadeRK. Nanocarriers assisted siRNA gene therapy for the management of cardiovascular disorders. Curr Pharm Des, 21: 4427–4440, 2015.
70.
ManeechoteC, PaleeS, ChattipakornSC, and ChattipakornN. Roles of mitochondrial dynamics modulators in cardiac ischaemia/reperfusion injury. J Cell Mol Med, 21: 2643–2653, 2017.
71.
MarosfoiMG, KorinN, GounisMJ, UzunO, VedanthamS, LanganET, PapaAL, BrooksOW, JohnsonC, PuriAS, BhattaD, KanapathipillaiM, BronsteinBR, ChuehJY, IngberDE, and WakhlooAK. Shear-activated nanoparticle aggregates combined with temporary endovascular bypass to treat large vessel occlusion. Stroke, 46: 3507–3513, 2015.
72.
MattoussiH and RotelloVM. Inorganic nanoparticles in drug delivery. Adv Drug Deliv Rev, 65: 605–606, 2013.
73.
MayfieldAE, TilokeeEL, LathamN, McNeillB, LamBK, RuelM, SuuronenEJ, CourtmanDW, StewartDJ, and DavisDR. The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function. Biomaterials, 35: 133–142, 2014.
74.
McAteerMA, AkhtarAM, von Zur MuhlenC, and ChoudhuryRP. An approach to molecular imaging of atherosclerosis, thrombosis, and vascular inflammation using microparticles of iron oxide. Atherosclerosis, 209: 18–27, 2010.
MekaruH, LuJ, and TamanoiF. Development of mesoporous silica-based nanoparticles with controlled release capability for cancer therapy. Adv Drug Deliv Rev, 95: 40–49, 2015.
77.
MorisD, SpartalisM, TzatzakiE, SpartalisE, KarachaliouGS, TriantafyllisAS, KaraolanisGI, TsilimigrasDI, and TheocharisS. The role of reactive oxygen species in myocardial redox signaling and regulation. Ann Transl Med, 5: 324, 2017.
78.
NishidaK and OtsuK. Inflammation and metabolic cardiomyopathy. Cardiovasc Res, 113: 389–398, 2017.
79.
NishikawaM, OgawaK, UmekiY, MohriK, KawasakiY, WatanabeH, TakahashiN, KusukiE, TakahashiR, TakahashiY, and TakakuraY. Injectable, self-gelling, biodegradable, and immunomodulatory DNA hydrogel for antigen delivery. J Control Release, 180: 25–32, 2014.
80.
OuimetT, LancelotE, HyafilF, RienzoM, DeuxF, LemaitreM, DuquesnoyS, GarotJ, RoquesBP, MichelJB, CorotC, and BalletS. Molecular and cellular targets of the MRI contrast agent P947 for atherosclerosis imaging. Mol Pharm, 9: 850–861, 2012.
81.
PagelsRF and Prud'hommeRK. Polymeric nanoparticles and microparticles for the delivery of peptides, biologics, and soluble therapeutics. J Control Release, 219: 519–535, 2015.
82.
ParkS, YoonJ, BaeS, ParkM, KangC, KeQ, LeeD, and KangPM. Therapeutic use of H2O2-responsive anti-oxidant polymer nanoparticles for doxorubicin-induced cardiomyopathy. Biomaterials, 35: 5944–5953, 2014.
83.
ParkYS.Preparation of concentrated colloids of gold core-silica shell nanoparticles for biomedical applications. Methods Mol Biol, 906: 21–31, 2012.
84.
PasutG.Pegylation of biological molecules and potential benefits: pharmacological properties of certolizumab pegol. BioDrugs, 28Suppl 1: S15–S23, 2014.
85.
PsarrosC, LeeR, MargaritisM, and AntoniadesC. Nanomedicine for the prevention, treatment and imaging of atherosclerosis. Nanomedicine, 8Suppl 1: S59–S68, 2012.
86.
QinH, ZhouT, YangS, ChenQ, and XingD. Gadolinium(III)-gold nanorods for MRI and photoacoustic imaging dual-modality detection of macrophages in atherosclerotic inflammation. Nanomedicine (Lond), 8: 1611–1624, 2013.
87.
RagelleH, DanhierF, PreatV, LangerR, and AndersonDG. Nanoparticle-based drug delivery systems: a commercial and regulatory outlook as the field matures. Expert Opin Drug Deliv, 14: 851–864, 2017.
88.
RenK, HeC, XiaoC, LiG, and ChenX. Injectable glycopolypeptide hydrogels as biomimetic scaffolds for cartilage tissue engineering. Biomaterials, 51: 238–249, 2015.
89.
RentropKP and FeitF. Reperfusion therapy for acute myocardial infarction: concepts and controversies from inception to acceptance. Am Heart J, 170: 971–980, 2015.
90.
SahooB, DeviKS, BanerjeeR, MaitiTK, PramanikP, and DharaD. Thermal and pH responsive polymer-tethered multifunctional magnetic nanoparticles for targeted delivery of anticancer drug. ACS Appl Mater Interfaces, 5: 3884–3893, 2013.
91.
SainzV, ConniotJ, MatosAI, PeresC, ZupancicE, MouraL, SilvaLC, FlorindoHF, and GasparRS. Regulatory aspects on nanomedicines. Biochem Biophys Res Commun, 468: 504–510, 2015.
92.
SalatinS, Maleki DizajS, and Yari KhosroushahiA. Effect of the surface modification, size, and shape on cellular uptake of nanoparticles. Cell Biol Int, 39: 881–890, 2015.
93.
SchienerM, HossannM, ViolaJR, Ortega-GomezA, WeberC, LauberK, LindnerLH, and SoehnleinO. Nanomedicine-based strategies for treatment of atherosclerosis. Trends Mol Med, 20: 271–281, 2014.
94.
SeshadriG, SyJC, BrownM, DikalovS, YangSC, MurthyN, and DavisME. The delivery of superoxide dismutase encapsulated in polyketal microparticles to rat myocardium and protection from myocardial ischemia-reperfusion injury. Biomaterials, 31: 1372–1379, 2010.
95.
ShangL, NienhausK, and NienhausGU. Engineered nanoparticles interacting with cells: size matters. J Nanobiotechnology, 12: 5, 2014.
96.
ShaoB, TangC, SinhaA, MayerPS, DavenportGD, BrotN, OdaMN, ZhaoXQ, and HeineckeJW. Humans with atherosclerosis have impaired ABCA1 cholesterol efflux and enhanced high-density lipoprotein oxidation by myeloperoxidase. Circ Res, 114: 1733–1742, 2014.
97.
ShengY, LiaoLD, ThakorNV, and TanMC. Nanoparticles for molecular imaging. J Biomed Nanotechnol, 10: 2641–2676, 2014.
98.
ShiZ, GuoR, LiW, ZhangY, XueW, TangY, and ZhangY. Nanoparticles of deoxycholic acid, polyethylene glycol and folic acid-modified chitosan for targeted delivery of doxorubicin. J Mater Sci Mater Med, 25: 723–731, 2014.
99.
SiafakaPI, Ustundag OkurN, KaravasE, and BikiarisDN. Surface modified multifunctional and stimuli responsive nanoparticles for drug targeting: current status and uses. Int J Mol Sci, 17: 1440, 2016.
100.
SiminiakT and KurpiszM. Myocardial replacement therapy. Circulation, 108: 1167–1171, 2003.
101.
SongJT, YangXQ, ZhangXS, YanDM, YaoMH, QinMY, and ZhaoYD. Composite silica coated gold nanosphere and quantum dots nanoparticles for X-ray CT and fluorescence bimodal imaging. Dalton Trans, 44: 11314–11320, 2015.
102.
SorescuD, WeissD, LassegueB, ClempusRE, SzocsK, SorescuGP, ValppuL, QuinnMT, LambethJD, VegaJD, TaylorWR, and GriendlingKK. Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation, 105: 1429–1435, 2002.
103.
SosnovikDE, GarangerE, AikawaE, NahrendorfM, FiguiredoJL, DaiG, ReynoldsF, RosenzweigA, WeisslederR, and JosephsonL. Molecular MRI of cardiomyocyte apoptosis with simultaneous delayed-enhancement MRI distinguishes apoptotic and necrotic myocytes in vivo: potential for midmyocardial salvage in acute ischemia. Circ Cardiovasc Imaging, 2: 460–467, 2009.
104.
SpuentrupE, FaustenB, KinzelS, WiethoffAJ, BotnarRM, GrahamPB, HallerS, KatohM, ParsonsECJr., ManningWJ, BuschT, GuntherRW, and BueckerA.Molecular magnetic resonance imaging of atrial clots in a swine model. Circulation, 112: 396–399, 2005.
105.
SugamuraK and KeaneyJFJr. Reactive oxygen species in cardiovascular disease. Free Radic Biol Med, 51: 978–992, 2011.
106.
SukJS, XuQ, KimN, HanesJ, and EnsignLM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev, 99: 28–51, 2016.
107.
TakagiH, MatsuiY, and SadoshimaJ. The role of autophagy in mediating cell survival and death during ischemia and reperfusion in the heart. Antioxid Redox Signal, 9: 1373–1381, 2007.
108.
TanakaM, MokhtariGK, TerryRD, BalsamLB, LeeKH, KofidisT, TsaoPS, and RobbinsRC. Overexpression of human copper/zinc superoxide dismutase (SOD1) suppresses ischemia-reperfusion injury and subsequent development of graft coronary artery disease in murine cardiac grafts. Circulation, 110: II200–II206, 2004.
109.
TarinC, CarrilM, Martin-VenturaJL, MarkuerkiagaI, PadroD, Llamas-GrandaP, MorenoJA, GarciaI, GenicioN, Plaza-GarciaS, Blanco-ColioLM, PenadesS, and EgidoJ. Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI. Sci Rep, 5: 17135, 2015.
110.
TemmeS, GrapentinC, QuastC, JacobyC, GrandochM, DingZ, OwenierC, MayenfelsF, FischerJW, SchubertR, SchraderJ, and FlogelU. Noninvasive imaging of early venous thrombosis by 19F magnetic resonance imaging with targeted perfluorocarbon nanoemulsions. Circulation, 131: 1405–1414, 2015.
111.
ThomasSC, Harshita, MishraPK, and TalegaonkarS. Ceramic nanoparticles: fabrication methods and applications in drug delivery. Curr Pharm Des, 21: 6165–6188, 2015.
112.
TylerPD and KangPM. Diagnostic and therapeutic nanoparticles in cardiovascular diseases. Curr Pharm Des, 21: 6070–6080, 2015.
113.
UndasA and AriensRA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol, 31: e88–e99, 2011.
114.
van der MeelR, FensMH, VaderP, van SolingeWW, Eniola-AdefesoO, and SchiffelersRM. Extracellular vesicles as drug delivery systems: lessons from the liposome field. J Control Release, 195: 72–85, 2014.
115.
VanderkooyA, ChenY, GonzagaF, and BrookMA. Silica shell/gold core nanoparticles: correlating shell thickness with the plasmonic red shift upon aggregation. ACS Appl Mater Interfaces, 3: 3942–3947, 2011.
116.
VarshosazJ and TaymouriS. Hollow inorganic nanoparticles as efficient carriers for siRNA delivery: a comprehensive review. Curr Pharm Des, 21: 4310–4328, 2015.
117.
VashistA and AhmadS. Hydrogels in tissue engineering: scope and applications. Curr Pharm Biotechnol, 16: 606–620, 2015.
118.
VllasaliuD, FowlerR, and StolnikS. PEGylated nanomedicines: recent progress and remaining concerns. Expert Opin Drug Deliv, 11: 139–154, 2014.
119.
WangXF, JinPP, TongZ, ZhaoYP, DingQL, WangDB, ZhaoGM, JingD, WangHL, and GeHL. MR molecular imaging of thrombus: development and application of a Gd-based novel contrast agent targeting to P-selectin. Clin Appl Thromb Hemost, 16: 177–183, 2010.
120.
WangY, ZhaoQ, HanN, BaiL, LiJ, LiuJ, CheE, HuL, ZhangQ, JiangT, and WangS. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine, 11: 313–327, 2015.
121.
WeiselJW and LitvinovRI. Mechanisms of fibrin polymerization and clinical implications. Blood, 121: 1712–1719, 2013.
122.
WeisslederR, NahrendorfM, and PittetMJ. Imaging macrophages with nanoparticles. Nat Mater, 13: 125–138, 2014.
123.
XuY, WangL, LiYK, and WangCQ. Oxidation and pH responsive nanoparticles based on ferrocene-modified chitosan oligosaccharide for 5-fluorouracil delivery. Carbohydr Polym, 114: 27–35, 2014.
124.
YamadaM, FooteM, and ProwTW. Therapeutic gold, silver, and platinum nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 7: 428–445, 2015.
125.
YaoX, LiuY, GaoJ, YangL, MaoD, StefanitschC, LiY, ZhangJ, OuL, KongD, ZhaoQ, and LiZ. Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction. Biomaterials, 60: 130–140, 2015.
126.
YiS, AllenSD, LiuYG, OuyangBZ, LiX, AugsornworawatP, ThorpEB, and ScottEA. Tailoring nanostructure morphology for enhanced targeting of dendritic cells in atherosclerosis. ACS Nano, 10: 11290–11303, 2016.
127.
YokoyamaM.Polymeric micelles as drug carriers: their lights and shadows. J Drug Target, 22: 576–583, 2014.
128.
YuQ, LeeCF, WangW, KaramanlidisG, KurodaJ, MatsushimaS, SadoshimaJ, and TianR. Elimination of NADPH oxidase activity promotes reductive stress and sensitizes the heart to ischemic injury. J Am Heart Assoc, 3: e000555, 2014.
129.
ZhangY, PetiboneD, XuY, MahmoodM, KarmakarA, CascianoD, AliS, and BirisAS. Toxicity and efficacy of carbon nanotubes and graphene: the utility of carbon-based nanoparticles in nanomedicine. Drug Metab Rev, 46: 232–246, 2014.
130.
ZylberbergC, GaskillK, PasleyS, and MatosevicS. Engineering liposomal nanoparticles for targeted gene therapy. Gene Ther, 24: 441–452, 2017.
