Rheumatoid arthritis microenvironment insights into treatment effect of nanomaterials

Atherosclerosis is considered one of the primary causes of cardiovascular diseases (CVDs). Unpredictable rupture of the vulnerable atherosclerotic plaques triggers adverse cardiovascular events such as acute myocardial syndrome and even sudden cardiac death. Therefore, assessing the vulnerability of atherosclerotic plaques and early intervention are of significance in reducing CVD mortality. Nanomedicine possesses tremendous advantages in achieving the integration of the diagnosis and therapy of atherosclerotic plaques because of its magnetic, optical, thermal, and catalytic properties. Based on the pathological characteristics of vulnerable plaques, stimuli‐responsive nanoplatforms and surface‐functionalized nanoagents are designed and have drawn great attention for accomplishing the precise imaging and treatment of vulnerable atherosclerotic plaques due to their superior properties, such as high bioavailability, lesion‐targeting specificity, on‐demand cargo release, and low off‐target damage. Here, the characteristics of vulnerable plaques are generalized, and some targeted strategies for boosting the accuracy of plaque vulnerability evaluation by imaging and the efficacy of plaque stabilization therapy (including antioxidant therapy, macrophage depletion therapy, regulation of lipid metabolism therapy, anti‐inflammation therapy, etc.) are systematically summarized. In addition, existing challenges and prospects in this field are discussed, and it is believed to provide new thinking for the diagnosis and treatment of CVDs in the near future.

Targeting the Microenvironment of Vulnerable Atherosclerotic Plaques: An Emerging Diagnosis and Therapy Strategy for Atherosclerosis

The rapid emergence of pathogenic bacteria poses a serious threat to global health. Notably, traditional antibiotic therapies suffer from the risk of strengthening bacterial drug resistance. Sonodynamic therapy (SDT) combining sonosensitizers and low-intensity ultrasound (US) has broadened the way towards treating drug-resistant bacteria. The allure of this therapy emerges from the capacity to focus the US energy on bacterial infection sites buried deep in tissues, locally activating the sonosensitizers to produce cytotoxic reactive oxygen species (ROS) with the ability to induce bacterial death. The past decade has witnessed the rapid development of antibacterial SDT owing to their excellent penetration, favorable biocompatibility and specific targeting ability. This review summarizes available sonosensitizers for antibacterial SDT, and digs into innovative biotechnologies to improve SDT efficiency, such as enhancing the targeting ability of sonosensitizers, image-guided assisted SDT, improvement of hypoxia and combination of SDT with other therapies. Finally, we conclude with the present challenges and provide insights into the future research of antibacterial SDT.

Recent developments of sonodynamic therapy in antibacterial application.

Atherosclerosis (AS) is a leading cause of vascular diseases that severely threats the human health due to the lack of efficient therapeutic methods. During the development and progress of AS, macrophages play critical roles, which are polarized into pro-inflammatory M1 phenotype to excrete abundant cytokines and overproduce reactive oxygen species (ROS), and take up excess amount of lipid to form foam cells. In this work, we developed a MnO2-based nanomedicine to re-educate macrophages for targeting AS therapy. The MnO2 was one-pot synthesized under mild condition, showing intrinsic catalase-mimic activity for self-oxygenation by using endogenous H2O2 as substrate. Moreover, the mesoporous structure as well as the abundant metal coordination sites in MnO2 structure facilitated the loading of an anti-AS drug of curcumin (Cur), achieving extraordinarily high drug loading capacity of 54%. Cur displayed a broad spectrum of anti-oxidant and anti-inflammatory capabilities to repolarize M1 macrophages into M2 phenotype, and the catalytic MnO2 recovered the function of lipid efflux transporter to remove lipid from cells by suppressing HIF-1α. Collectively, the nanocarrier and the payload drug functioned as an all-active nanoplatform to synergistically alleviate the syndromes of AS. In ApoE-/- mice model, the nanosystem could significantly prolong the circulation half-life of Cur by sixfold, and enhance drug accumulation in atherosclerotic lesion by 3.5-fold after intravenous injection by virtue of surface hyaluronic acid (HA) modification. As a result, a robust anti-AS efficacy was achieved as evidenced by the decrease of atherosclerotic lesion, plaque area, lipid level. 

/pdf/self-oxygenation-mesoporous-mno2-nanoparticles-with-ultra-q9dbdee7.pdf

Self-oxygenation mesoporous MnO2 nanoparticles with ultra-high drug loading capacity for targeted arteriosclerosis therapy

In this work, a fluoroquinolone antibiotic drug (sparfloxacin (SP)) was selected as a chemotherapy drug and photosensitizer for combined therapy. A facile chemical process was developed to incorporate SP and upconversion nanoparticles (UCNPs) into the thermally sensitive amphiphilic polymer polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane). In vitro and in vivo experiments showed that 60% of the SP molecules can be released from the micelles of thermal-sensitive polymers using a 1 W cm-2 980 nm laser, and this successfully inhibits cell migration and metastasis by inhibiting type II topoisomerases in nuclei. Additionally, intracellular metal ions were chelated by SP to induce cancer cell apoptosis by decreasing the activity of superoxide dismutase and catalase. In particular, the fluoroquinolone molecules produced singlet oxygen (1O2) to kill cancer cells, and this was triggered by UCNPs when irradiation was performed with a 980 nm laser. Overall, SP retained a weak chemotherapeutic effect, achieved enhanced photosensitizer-like effects, and was able to repurpose old drugs to elevate the therapeutic efficacy against cancer, increase the specificity for suppressing tumor migration and proliferation, and enhance apoptosis.

Phototherapy Using a Fluoroquinolone Antibiotic Drug to Suppress Tumor Migration and Proliferation and to Enhance Apoptosis.

Mutual-reinforcing sonodynamic therapy against Rheumatoid Arthritis based on sparfloxacin sonosensitizer doped concave-cubic rhodium nanozyme.

Palladium Hydride Nanopocket Cubes and Their H2-Therapy Function in Amplifying Inhibition of Foam Cells to Attenuate Atherosclerosis

Platinum-cerium bimetallic nano-raspberry for atherosclerosis treatment via synergistic foam cell inhibition and P2Y12 targeted antiplatelet aggregation

Xiaoyang Liang

Papers

Mutual-reinforcing sonodynamic therapy against Rheumatoid Arthritis based on sparfloxacin sonosensitizer doped concave-cubic rhodium nanozyme.

Palladium Hydride Nanopocket Cubes and Their H2-Therapy Function in Amplifying Inhibition of Foam Cells to Attenuate Atherosclerosis

Platinum-cerium bimetallic nano-raspberry for atherosclerosis treatment via synergistic foam cell inhibition and P2Y12 targeted antiplatelet aggregation

Enhanced macrophage polarization induced by COX-2 inhibitor-loaded Pd octahedral nanozymes for treatment of atherosclerosis

Sequential delivery for hepatic fibrosis treatment based on carvedilol loaded star-like nanozyme.