Chemotactic NO/H₂S Nanomotors Realizing Cardiac Targeting of G-CSF against Myocardial Ischemia-Reperfusion Injury

Abstract

Recombinant granulocyte colony-stimulating factor (G-CSF), with a direct repair effect on injured cardiomyocytes against myocardial infarction ischemia-reperfusion-injury (IRI), displays a poor effect owing to the limited cardiac targeting efficacy. There are almost no reports of nanomaterials that deliver G-CSF to the IRI site. Herein, we propose a way to protect G-CSF by constructing one layer of nitric oxide (NO)/hydrogen sulfide (H2S) nanomotors on its outside. NO/H2S nanomotors with specific chemotactic ability to high expression of reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) at the IRI site can deliver G-CSF to the IRI site efficiently. Meanwhile, superoxide dismutase is covalently bound to the outermost part, reducing ROS at the IRI site through a cascade effect with NO/H2S nanomotors. The synergistic effect between NO and H2S on the effective regulation of the IRI microenvironment can not only avoid toxicity caused by excessive concentration of a single gas but also reduce inflammation level and relieve calcium overload, so as to promote G-CSF to play a cardioprotective role.

Progress in the Treatment of Peritoneal Metastatic Cancer and the Application of Therapeutic Nanoagents

“…In recent years, therapeutic nanoagents with different substrates have been developed to alleviate these deficiencies, but these therapeutic nanoagents are unable to overcome problems including passive cellular uptake, penetration of biological barriers (peritoneal-plasma barrier), etc. Recently, a nanomotor technology with rapid research development may be the solution to the above problems. − This is because nanomotors have the ability to move autonomously that conventional nanomaterials do not have, which makes them more penetrating and able to actively promote its uptake by cells as well as penetrate the peritoneal–plasma barrier. , For example, Wan et al reported an H 2 S-driven nanomotor in 2021. This nanomotor can significantly improve its permeability in tissues due to its unique motility and specifically inhibit tumor growth by disrupting tumor metabolic symbiosis .…”

Chemotactic Micro/Nanomotors for Biomedical Applications

“…Breast cancer [116] Pd NPs / [123] Tz-HAp nanorods Cancer cells [133] NM-si Breast cancer [134] PDA-MC Stomach cancer [135] PDA@HSA@Ur@DOX Cancer cells [136] MSNPs Medical imaging [137] CD-LA-Au-aV Atherosclerosis [138] PMA-TPP/PTX Atherosclerosis [139] SOD/PAC@CSF Ischemia reperfusion injury [144] TME, researchers have developed different chemotactic targeting delivery systems to enhance tumor targeting and improve cancer therapeutic efficacy, respectively. For example, Chen et al [106] reported a Janus engineered mitochondrion modified with GOx and polymers to achieve self-driven and chemotaxis-based deep tumor penetration in tumor tissues via GOx catalysis of glucose, showing good tumorsphere penetration and tumor targeting (Figure 16B).…”

“…[143] However, its targeting ability towards the heart is limited, and the therapeutic effect is poor. Based on this challenge, Li et al [144] designed a NO/H 2 S nanomotor that can [138] Copyright 2021, Wiley-VCH GmbH. B) Schematic diagram of the preparation of lipophilic nanomotors and PMA-TPP/PTX nanomotors as drug balloon coatings for the treatment of AS.…”

“…Figure 25.A) The preparation of NO/H 2 S SOD/PAC@CSF nanomotors; B) chemotaxis, reactive drug release, and the treatment of IRI by NO/H 2 S SOD/PAC@CSF nanomotors in the disease microenvironment. Reproduced with permission [144]. Copyright 2023, American Chemical Society.…”

Personalized SO2 Prodrug for pH-Triggered Gas Enhancement in Anti-Tumor Radio-Immunotherapy

“…Gas therapy, emerging as a novel treatment strategy, is currently garnering significant attention. By leveraging the physical and chemical properties of nanoplatforms, which generate therapeutic gases like hydrogen (H 2 ) [ 1 , 2 ], sulfur dioxide (SO 2 ) [ 3 , 4 ], hydrogen sulfide (H 2 S) [ 5 , 6 ], and nitric oxide (NO) [ 7 , 8 , 9 ] through prodrug activation and donation, gas therapy demonstrates promise in modulating the physiological and chemical conditions to treat various diseases, such as inflammation, cardiac ischemia-reperfusion, and cancer [ 10 , 11 , 12 ]. In tumor therapy, nanoplatforms that generate SO 2 within tumors can effectively address tumor heterogeneity, leading to tumor eradication.…”