Nanomaterials-Mediated Therapeutics and Diagnosis Strategies for Myocardial Infarction

Abstract

The alarming mortality and morbidity rate of myocardial infarction (MI) is becoming an important impetus in the development of early diagnosis and appropriate therapeutic approaches, which are critical for saving patients' lives and improving post-infarction prognosis. Despite several advances that have been made in the treatment of MI, current strategies are still far from satisfactory. Nanomaterials devote considerable contribution to tackling the drawbacks of conventional therapy of MI by improving the homeostasis in the cardiac microenvironment via targeting, immune modulation, and repairment. This review emphasizes the strategies of nanomaterials-based MI treatment, including cardiac targeting drug delivery, immune-modulation strategy, antioxidants and antiapoptosis strategy, nanomaterials-mediated stem cell therapy, and cardiac tissue engineering. Furthermore, nanomaterials-based diagnosis strategies for MI was presented in term of nanomaterials-based immunoassay and nano-enhanced cardiac imaging. Taken together, although nanomaterials-based strategies for the therapeutics and diagnosis of MI are both promising and challenging, such a strategy still explores the immense potential in the development of the next generation of MI treatment.

Keywords: diagnosis; macrophage; myocardial infarction; nanomaterials; targeted delivery.

FIGURE 1

Schematic overview of the advances of nanomaterials and applications for both therapeutics and diagnosis.

FIGURE 2

Applying antibody-conjugated magnetic nanoparticles for the targeting delivery in the treatment of MI. Magnetic antibody-linked nanomatchmakers for therapeutic stem cell targeting in the treatment of MI. (A) Schematic representations of the cell matchmaking by magnetic bifunctional cell engager 1 (MagBICE) and the preparation of MagBICE nanoparticles. (B) Fluorescent microscopic images showing the binding of MagBICE₁, but not unconjugated Feraheme (FH), to rat bone marrow mononuclear cells (BMCs). (C) Fluorescent microscopic images showing MagBICE₁ conjoined BMCs (DiD-labelled, magenta) with injured cardiomyocytes, Adapted with permission from Cheng et al., 2014. (D) Schematic representations of vesicle shuttle which can effectively collect, transport, and release circulating exosomes to infarcted areas of the hearts by the core-shell-corona structure by applying antibody-conjugated magnetic nanoparticles. (E) Schematic of the GMNP fabrication. (F) Schematic of the construction of endothelial cell denoted surface-grafted magnetic nanoparticles (GMNP_EC) by the addition of anti-CD63 and anti-myosin light chain (MLC) antibodies to GMNPs, and the attachment of rat-derived exosomes from the in vitro serum to the anti-CD63 on the surface of GMNP_EC nanoparticles (GMNP_EC–EXO). (G) Ex vivo fluorescent imaging of intravenously (i.v.) injected RhB-labelled GMNPN in MI-model rats with or without subsequent exposure to an external magnetic field. Adapted with permission from Liu et al., 2020.

FIGURE 3

Nanomaterials use immune-modulation strategy to treat MI. (A) Chemical construction of PP/PS@MIONs nanotheranostic system by the thin-film dispersion method. (B) Schematic illustration for PP/PS@MIONs in MI. PP/PS@MIONs were accumulated in the MI area due to magnetic targeting and PS targeting and promoted the differentiation of the pro-inflammatory macrophages (M1) into the reparative macrophages (M2). (C) Representative MR images of hearts before and 24 h after i. v. administration of PP/PS@MIONs and PP@MIONs with or without a magnet. Adapted with permission from Chen et al., 2017. (D) Schematic illustration of MI treatment using liposomal nanoparticles loaded with MI-associated antigens and rapamycin (L-Ag/R). (E) The delivery of L-Ag/R promoted the antigen presentation efficiency of DCs, inhibited the expressions of co-stimulatory surface molecules and pro-inflammatory cytokines expression in DCs, and increased the expressions of anti-inflammatory cytokines in DCs. Adapted with permission from Kwon et al., 2021.

FIGURE 4

The application of nanomaterials for the delivery of miRNA and pDNA to inhibit the cardiomyocytes apoptosis in MI. (A) Schematic illustration of the construction of unlockable heparin core-shell nanocomplexes (Hep@PGEA) and their applications in the delivery of miRNA and pDNA for the treatment of MI. (B) The time axis of this study and the evaluation of GSH amount in mouse hearts at different time points after MI. (C) Hep@PGEA preserved the cardiac function of mice after MI evaluated by M-mode echocardiograms. (D) The delivery of Hep@PGEA reduced the infarct areas and fibrosis areas reflected by quantification of Masson trichrome and Red Sirius staining. (E) Hep@PGEA inhibited the cardiomyocytes hypertrophy reflected by the WGA staining. Adapted with permission from Nie et al., 2018.

FIGURE 5

The strategy of nanomaterials assistant stem cell therapy for MI. (A) Schematic illustration of the poly (lactic-co-glycolic acid) (PLGA) fabricated aligned nanofibers (ANFs) for the high-quality cardiac tissue-like constructs (CTLCs) differentiated from human induced pluripotent stem cells (hiPSCs). (B) The construction of PLGA-mediated ANFs and their effects on the 3D cardiac tissue-like constructs (CTLCs). (C) Schematic representation of CTLCs on the microelectrode array (MEA) and a representative electrogram of the field potential (FP). Activation maps showing the propagation of stimulated contractility on day 6. (D) CTLCs synchronize disconnected cardiomyocyte tissues and suppress re-entrant arrhythmia within scarred cardiomyocyte sheets. (E) Histological sections of CTLCs on the MI tissues cultured by aligned nanofibers and acellular nanofibers, respectively. Adapted with permission from Li et al., 2017.

FIGURE 6

Mussel-inspired conductive cryogel as a promising strategy for the restoration of infarcted myocardium. (A) Schematic illustration of the mussel-inspired conductive cryogel for engineered cardiac tissue patch in rat MI models. (B) Characterization and ultrastructure of the DOPA-based Ppy PEG-gelatin cryogel. (C) The DOPA-based MA-G/PEGDA/Ppy cryogel showed higher protein expressions of α-actinin and CX-43 in the cardiomyocytes presented by immunofluorescent staining. (D) The DOPA-based MA-G/PEGDA/Ppy cryogel significantly improved the cardiac functions of the mice after MI. Adapted with permission from Wang et al., 2016.

FIGURE 7

Nano-biosensor based on electrochemical or photoelectrochemical for the detection of MI-related indicators. (A) Schematic illustration for the fabrication processes of the AuNPs/BNNSs nanosheets and the detection of myoglobin (Mb). (B) Electrochemical characterization of AuNPs/BNNSs nanosheets. (C) Detection of Mb and interference studies, stability, reproducibility, and real-sample analyses of AuNPs/BNNSs nanosheets. Adapted with permission from Adeel et al., 2019. (D) The mechanism of the carbon dots nano-biosensor based on photoelectrochemical for the detection of glutathione (GSH). (E) Sensitivity and photocurrents the carbon dots-based biosensors introducing silver nanoparticles, graphene oxide, and mesoporous silica. Adapted with permission from Li et al., 2018.

FIGURE 8

MnO₂/Gd₂O₃ nanocomposites used as a contrasting agent for MRI bioimaging modalities for sensitive detection of MI. (A) Schematic illustration of MnO₂@BSA and Gd₂O₃@BSA nanocomposites for MR imaging of MI in rabbit models, the MnO₂@BSA nanocomposites could be accumulated in MI regions and response to the low pH to liberate Mn²⁺ to achieve specific contrast enhancement for MR imaging of MI. (B) MR imaging of acute myocardium infarction in rabbits contrasted by Gd₂O₃@BSA nanocomposites. (C) MR imaging of acute myocardium infarction in rabbits contrasted by MnO₂@BSA nanocomposites. Adapted with permission from Wang et al., 2020.