Cardiovascular diseases (CVDs) remain one of the major causes of mortality worldwide. In response to this and other worldwide health epidemics, nanomedicine has emerged as a rapidly evolving discipline that involves the development of innovative nanomaterials and nanotechnologies and their applications in therapy and diagnosis. Nanomedicine presents unique advantages over conventional medicines due to the superior properties intrinsic to nanoscopic therapies. Once used mainly for cancer therapies, recently, tremendous progress has been made in nanomedicine that has led to an overall improvement in the treatment and diagnosis of CVDs. This review elucidates the pathophysiology and potential targets of atherosclerosis and associated ischemic diseases. It may be fruitful to pursue future work in the nanomedicine‐mediated treatment of CVDs based on these targets. A comprehensive overview is then provided featuring the latest preclinical and clinical outcomes in cardiovascular imaging, biomarker detection, tissue engineering, and nanoscale delivery, with specific emphasis on nanoparticles, nanostructured scaffolds, and nanosensors. Finally, the challenges and opportunities regarding the future development and clinical translation of nanomedicine in related fields are discussed. Overall, this review aims to provide a deep and thorough understanding of the design, application, and future development of nanomedicine for atherosclerosis and related ischemic diseases.
Ionizable cationic lipid-containing
lipid nanoparticles (LNPs)
are the most clinically advanced non-viral gene delivery platforms,
holding great potential for gene therapeutics. This is exemplified
by the two COVID-19 vaccines employing mRNA-LNP technology from Pfizer/BioNTech
and Moderna. Herein, we develop a chemical library of ionizable cationic
lipids through a one-step chemical-biological enzyme-catalyzed esterification
method, and the synthesized ionizable lipids were further prepared
to be LNPs for mRNA delivery. Through orthogonal design of experiment
methodology screening, the top-performing AA3-DLin LNPs show outstanding
mRNA delivery efficacy and long-term storage capability. Furthermore,
the AA3-DLin LNP COVID-19 vaccines encapsulating SARS-CoV-2 spike
mRNAs successfully induced strong immunogenicity in a BALB/c mouse
model demonstrated by the antibody titers, virus challenge, and T
cell immune response studies. The developed AA3-DLin LNPs are an excellent
mRNA delivery platform, and this study provides an overall perspective
of the ionizable cationic lipids, from aspects of lipid design, synthesis,
screening, optimization, fabrication, characterization, and application.
Interleukin-11 (IL-11) is a profibrotic cytokine essential for the differentiation of fibroblasts into collagen-secreting, actin alpha 2, smooth muscle–positive (ACTA2
+
) myofibroblasts, driving processes underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF). Here, we developed an inhalable and mucus-penetrative nanoparticle (NP) system incorporating siRNA against
IL11
(si
IL11
@PPGC NPs) and investigated therapeutic potential for the treatment of IPF. NPs are formulated through self-assembly of a biodegradable PLGA-PEG diblock copolymer and a self-created cationic lipid-like molecule G0-C14 to enable efficient transmucosal delivery of si
IL11
. Noninvasive aerosol inhalation hindered fibroblast differentiation and reduced ECM deposition via inhibition of ERK and SMAD2. Furthermore, si
IL11
@PPGC NPs significantly diminished fibrosis development and improved pulmonary function in a mouse model of bleomycin-induced pulmonary fibrosis without inducing systemic toxicity. This work presents a versatile NP platform for the locally inhaled delivery of siRNA therapeutics and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including IPF.
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