Cardiomyocyte-targeted anti-inflammatory nanotherapeutics against myocardial ischemia reperfusion (IR) injury

Abstract

Myocardial ischemia reperfusion (IR) injury is closely related to the overwhelming inflammation in the myocardium. Herein, cardiomyocyte-targeted nanotherapeutics were developed for the reactive oxygen species (ROS)-ultrasensitive co-delivery of dexamethasone (Dex) and RAGE small interfering RNA (siRAGE) to attenuate myocardial inflammation. PPTP, a ROS-degradable polycation based on PGE 2 -modified, PEGylated, ditellurium-crosslinked polyethylenimine (PEI) was developed to surface-decorate the Dex-encapsulated mesoporous silica nanoparticles (MSNs), which simultaneously condensed siRAGE and gated the MSNs to prevent the Dex pre-leakage. Upon intravenous injection to IR-injured rats, the nanotherapeutics could be efficiently transported into the inflamed cardiomyocytes via PGE 2 -assisted recognition of over-expressed E-series of prostaglandin (EP) receptors on the cell membranes. Intracellularly, the over-produced ROS degraded PPTP into small segments, promoting the release of siRAGE and Dex to mediate effective RAGE silencing (72%) and cooperative antiinflammatory effect. As a consequence, the nanotherapeutics notably suppressed the myocardial fibrosis and apoptosis, ultimately recovering the systolic function. Therefore, the current nanotherapeutics represent an effective example for the co-delivery and on-demand release of nucleic acid and chemodrug payloads, and might find promising utilities toward the synergistic management of myocardial inflammation. Electronic Supplementary Material Supplementary material (experimental methods, RNA and primer sequences, 1 H NMR spectra, FTIR spectrum, TEM images, zeta potential, drug loading content, RNA and drug release, cytotoxicity, etc.) is available in the online version of this article at 10.1007/s12274-022-4553-6.

Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease

“…The DSP curve exhibited strong peaks at 1713 and 1629 cm −1 , consistent with previous literature reports. 18,19 The Ce-MOFs curve displayed characteristic peaks at 1641−1554 cm −1 and 1435−1373 cm −1 , corresponding to the asymmetric and symmetric stretching vibrations of the carboxylate ion, respectively. The observed vibrations in the raw material H 2 BDC were attributed to the presence of a carboxyl group (−OCO−).…”

Cysteine-Based Redox-Responsive Nanoparticles for Fibroblast-Targeted Drug Delivery in the Treatment of Myocardial Infarction

“…The lack of an effective drug carrier that can reach and accumulate in the injured heart and then selectively release its payload to the activated CFs represents a key barrier to the pharmacological intervention of cardiac fibrosis . Most recently, although two studies have demonstrated the feasibility of redox-sensitive NPs for heart-targeted repair after MI, , it should be noted that CF-selective drug delivery capable of treating cardiac fibrosis remains unaccomplished. Here, we report the finding of Cys-based redox-responsive NPs as activated CF-targeted drug carriers.…”

Photodynamic therapy for prostate cancer: Recent advances, challenges and opportunities

“…Due to the poor tissue penetration depth of excitation lights, the penetration depth of green or blue light is only 2 mm, which is not enough for deep tumors. Therefore, there is an urgent need to find out some new strategies to produce ROS under external stimulation with high penetrability (110). Several thirdgeneration of PSs can respond to external excitations such as NIR light, ultrasound, X-ray, chemiluminescent, bioluminescent sources, Cherenkov radiation, and implants (111).…”