Showing papers by "Yi Yan Yang published in 2023"

Gastric Acid-Responsive ROS Nanogenerators for Effective Treatment of Helicobacter pylori Infection without Disrupting Homeostasis of Intestinal Flora.

Abstract: Helicobacter pylori (H. pylori) has infected more than half of the world's population, and is the major cause of gastric cancer. The efficacy of standard antibiotic-based triple therapy is declining due to drug resistance development. Herein, a pH-responsive reactive oxygen species (ROS) nanogenerator (Fe-HMME@DHA@MPN) composed of acid-responsive metal polyphenol network (MPN) shell and mesoporous metal-organic nanostructure core [Fe-HMME (hematoporphyrin monomethyl ether, sonosensitizer)] loaded with dihydroartemisinin (DHA) is reported. These nanoparticles generate more ROS singlet oxygen than sonosensitizer HMME under ultrasonication, and this sonodynamic process is fueled by oxygen generated through Fenton/Fenton-like reactions of the degraded product in gastric acid Fe (II) and hydrogen peroxide (H2 O2 ) in the infection microenvironment. The encapsulated DHA, as a hydroperoxide source, is found to enhance the peroxidase-like activity of the Fe-HMME@DHA@MPN to generate ROS hydroxyl radical, beneficial for the microenvironment without sufficient H2 O2 . In vitro experiments demonstrate that the ROS nanogenerators are capable of killing multidrug-resistant H. pylori and removing biofilm, and ROS nanogenerators show high therapeutic efficacy in a H. pylori infection mouse model. Unlike the triple therapy, the nanogenerators display negligible side effects toward the normal gut microbiota. Taken together, these self-enhanced ROS nanogenerators have a great potential for treatment of H. pylori infection.

Water-Mediated In Situ Fabrication of CuI Nanoparticles on Flexible Cotton Fabrics as a Sustainable and Skin-Compatible Coating with Broad-Spectrum Antimicrobial Efficacy

Abstract: Infectious pathogens, such as SARS-CoV-2, can remain viable on common fabric surfaces for days, posing a significant risk of fomite transmission. Antimicrobial coatings are a widely employed approach for pathogen eradication upon direct contact. However, fabricating such coatings on fabric substrates mostly necessitates toxic organic solvents and complex equipment/procedures. Most coatings also require a long contact time for complete disinfection, which may compromise their usefulness in mitigating the spread of highly infectious pathogens. Herein, we report a sustainable and scalable water-mediated method to prepare a copper iodide (CuI) coating on flexible cotton fabrics, attaining highly potent antimicrobial efficacy and rapid germicidal kinetics. Only water is required as the processing solvent for the in situ formation of CuI nanoparticles on the substrate, and the unconsumed reagents can be fully recycled, making the reported method a green, economical, and zero-waste technology promising for industrial scale-up. Within just 2 min of contact, the coated cotton fabric containing 5.1 wt % CuI nanoparticles exhibits near-complete inactivation of murine hepatitis coronavirus (>99.9%) and Salmonella bacteriophage P22 (>99.9999%) as models for the enveloped and nonenveloped viral species, respectively. It is also able to eliminate a variety of bacteria and fungi with 3.5–7.4 log reductions in 2–5 min. Furthermore, in view of the robust durability and skin compatibility of the coating, this simple yet powerful approach holds great promise for practical applications, especially in future infectious disease outbreaks.

Encapsulation of Nano-Bortezomib in Apoptotic Stem Cell-Derived Vesicles for the Treatment of Multiple Myeloma.

Abstract: Extracellular vesicles (EVs) are lipid bilayer nanovesicles released from living or apoptotic cells that can transport DNA, RNA, protein, and lipid cargo. EVs play critical roles in cell-cell communication and tissue homeostasis, and have numerous therapeutic uses including serving as carriers for nanodrug delivery. There are multiple ways to load EVs with nanodrugs, such as electroporation, extrusion, and ultrasound. However, these approaches may have limited drug-loading rates, poor EV membrane stability, and high cost for large-scale production. Here, it is shown that apoptotic mesenchymal stem cells (MSCs) can encapsulate exogenously added nanoparticles into apoptotic vesicles (apoVs) with a high loading efficiency. When nano-bortezomib is incorporated into apoVs in culture-expanded apoptotic MSCs, nano-bortezomib-apoVs show a synergistic combination effect of bortezomib and apoVs to ameliorate multiple myeloma (MM) in a mouse model, along with significantly reduced side effects of nano-bortezomib. Moreover, it is shown that Rab7 regulates the nanoparticle encapsulation efficiency in apoptotic MSCs and that activation of Rab7 can increase nanoparticle-apoV production. In this study, a previously unknown mechanism to naturally synthesize nano-bortezomib-apoVs to improve MM therapy is revealed.

Neutrophil-inspired photothermo-responsive drug delivery system for targeted treatment of bacterial infection and endotoxins neutralization

Abstract: P. aeruginosa, a highly virulent Gram-negative bacterium, can cause severe nosocomial infections, and it has developed resistance against most antibiotics. New therapeutic strategies are urgently needed to treat such bacterial infection and reduce its toxicity caused by endotoxin (lipopolysaccharide, LPS). Neutrophils have been proven to be able to target inflammation site and neutrophil membrane receptors such as Toll-like receptor-4 (TLR4) and CD14, and exhibit specific affinity to LPS. However, antibacterial delivery system based on the unique properties of neutrophils has not been reported.A neutrophil-inspired antibacterial delivery system for targeted photothermal treatment, stimuli-responsive antibiotic release and endotoxin neutralization is reported in this study. Specifically, the photothermal reagent indocyanine green (ICG) and antibiotic rifampicin (RIF) are co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-ICG/RIF), followed by coating with neutrophil membrane to obtain antibacterial delivery system (NM-NP-ICG/RIF). The inflammation targeting properties, synergistic antibacterial activity of photothermal therapy and antibiotic treatment, and endotoxin neutralization have been studied in vitro. A P. aeruginosa-induced murine skin abscess infection model has been used to evaluate the therapeutic efficacy of the NM-NP-ICG/RIF.Once irradiated by near-infrared lasers, the heat generated by NP-ICG/RIF triggers the release of RIF and ICG, resulting in a synergistic chemo-photothermal antibacterial effect against P. aeruginosa (~ 99.99% killing efficiency in 5 min). After coating with neutrophil-like cell membrane vesicles (NMVs), the nanoparticles (NM-NP-ICG/RIF) specifically bind to inflammatory vascular endothelial cells in infectious site, endowing the nanoparticles with an infection microenvironment targeting function to enhance retention time. Importantly, it is discovered for the first time that NMVs-coated nanoparticles are able to neutralize endotoxins. The P. aeruginosa murine skin abscess infection model further demonstrates the in vivo therapeutic efficacy of NM-NP-ICG/RIF.The neutrophil-inspired antibacterial delivery system (NM-NP-ICG/RIF) is capable of targeting infection microenvironment, neutralizing endotoxin, and eradicating bacteria through a synergistic effect of photothermal therapy and antibiotic treatment. This drug delivery system made from FDA-approved compounds provides a promising approach to fighting against hard-to-treat bacterial infections.

Nanocomplexes of Biodegradable Anticancer Macromolecules: Prolonged Plasma Half-life, Reduced Toxicity, and Increased Tumor Targeting.

Abstract: Anticancer drug resistance is a large contributing factor to the global mortality rate of cancer patients. Anticancer macromolecules such as polymers were recently reported to overcome this issue. Anticancer macromolecules have unselective toxicity because they are highly positively charged. Herein, an anionic biodegradable polycarbonate carrier was synthesized and utilized to form nanocomplexes with an anticancer polycarbonate via self-assembly to neutralize its positive charges. Biotin was conjugated to the anionic carrier and served as a cancer cell-targeting moiety. The nanoparticles had sizes of <130 nm with anticancer polymer loading levels of 38%-49%. Unlike the small molecular anticancer drug doxorubicin, the nanocomplexes effectively inhibited the growth of both drug-susceptible MCF7 and drug-resistant MCF7/ADR human breast cancer cell lines with low half maximal inhibitory concentration (IC50 ). The nanocomplexes increased the anticancer polymer's in vivo half-life from 1 h to 6 - 8 h, and rapidly killed BT474 human breast cancer cells primarily via an apoptotic mechanism. The nanocomplexes significantly increased the median lethal dose (LD50) and reduced the injection site toxicity of the anticancer polymer. They suppressed tumor growth by 32% - 56% without causing any damage to the liver and kidneys. These nanocomplexes may potentially be used for cancer treatment to overcome drug resistance. This article is protected by copyright. All rights reserved.