Nanomaterials Responsive to Endogenous Biomarkers for Cardiovascular Disease Theranostics

Abstract

Cardiovascular disease (CVD) is the number one cause of death worldwide, which propels the development of advanced technologies for CVD diagnosis and treatment. Biomarker-responsive nanomaterials are appealing therapeutic platforms that provide new horizons for CVD theranostics. In this review, recent advances in nanomaterials with endogenous biomarkers as stimuli or targets for CVD theranostics is presented. First, the categories of biomarkers involved are comprehensively itemized based on pathological mechanisms including pH, reactive oxygen species, lipids, enzymes, macrophage receptors, subendothelium components, platelet receptors, inflammation, and osteopontin. The role of these biomarkers in bridge-building between nanomaterials and CVD is then presented. Next, the biomedical applications of nanomaterials responsive to endogenous biomarkers as stimuli or targets for the diagnosis and treatment of CVD are elaborated. Finally, the challenges and future research directions of biomarker-responsive nanomaterials in CVD are also discussed. This review will provide scientific guidance to facilitate clinical applications of biomarker-responsive nanomaterials.

Activatable Probes for Ratiometric Imaging of Endogenous BiomarkersIn Vivo

“…Enzymes, such as matrix metalloproteinase-2 (MMP-2), are essential in numerous physiological and pathological processes, and play a significant role in the pathophysiology of diseases including inflammation, cancer development, and infection. Abnormal enzymatic activity is associated with the pathogenesis of such diseases. − Specifically, MMP-2 has been identified as an important biomarker for the invasion and metastasis of malignant tumors, with implications in ovarian, lung, and gastric cancer. Ascertaining enzymatic activity in vivo is therefore critical for both diagnosis and therapy of tumors. − Gao et al designed a MMP-2-responsive probe (QSY21-GPLGVRGY-Cy5.5) for the quantitative detection of MMP-2 in vivo through ratiometric PA imaging (Figure a) .…”

Precise diagnosis of cardiac‐cerebral vascular diseases with magnetic resonance imaging‐based nanoprobes

“…For example, Gao and Lou et al used Arg-Gly-Asp (RGD) peptide to modify iron oxide nanoparticles (Fe 3 O 4 -RGD) for visualizing the collaterals occurring during acute ischemic stroke via integrin α v β 3 [53]. The obvious enhancement effects on the collaterals were observed over 24 h after the injection of Fe 3 O 4 -RGD nanoprobes, which was much longer than obtained with the mother particle or the control group, or prior to the injection of Fe iRADIOLOGY microenvironments, such as overexpression of proteases, increased secretion of inflammatory cytokines, recruitment of immune cells, alterations in vascular smooth muscle cells (VSMCs), and abnormal environmental factors such as acidic pH and increased reactive oxygen species, provide a rich source of targets for designing specific imaging probes [54]. Proteinases, as a crucial component of microenvironments, including thrombin [55], matrix metalloproteinases [56][57][58][59][60][61][62], and cathepsin cysteine proteases [63][64][65], exhibit altered expression levels during the progression of CCVDs.…”

Nanomaterials for Disease Treatment by Modulating the Pyroptosis Pathway

“…[ 100 ] In addition to the acidic TME‐responsive nanomaterials, reactive oxygen species (ROS)‐responsive nanomaterials can also be an excellent medium to activate tumor pyroptosis. [ 101,102 ] For example, Zhao et al. designed a ROS‐responsive implantable bio‐responsive nanoarray (DOX/JQ1‐IBRNs) consisting of DOX‐alpha epigenetic modulator JQ1 and hyaluronic acid (HA)‐modified polydopamine nanoparticles (HA‐PDA, HP NPs) for effectively inhibiting tumor growth, recurrence, and metastasis by pyroptosis pathway (Figure 3G,H).…”