RESUMEN
Introduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses. Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy. Herein, we engineered an iron-based nanoplatform termed ERFe3O4 NPs. This platform features hollow Fe3O4 nanoparticles loaded with the natural product emodin, the outer layer is coated with red blood cell membrane (mRBCs) inserted with DSPE-PEG2000-galactose. This effectively modulates lactate production, thereby reversing the tumor immune suppressive microenvironment (TIME). Results: The ERFe3O4 NPs actively targeted TAMs on account of their ability to bind to M2-like TAMs with high expression of galectin (Mgl). ERFe3O4 NPs achieved efficient ability to reverse TIME via the production of reducing lactate and prompting enrichment iron of high concentrations. Furthermore, ERFe3O4 NPs resulted in heightened expression of CD16/32 and enhanced TNF-α release, indicating promotion of M1 TAMs polarization. In vitro and in vivo experiments revealed that ERFe3O4 NPs induced significant apoptosis of tumor cells and antitumor immune response. Discussion: This study combines Traditional Chinese Medicine (TCM) with nanomaterials to synergistically reprogram TAMs and reverse TIME, opening up new ideas for improving anti-tumor immunotherapy.
Asunto(s)
Inmunoterapia , Microambiente Tumoral , Microambiente Tumoral/efectos de los fármacos , Animales , Inmunoterapia/métodos , Ratones , Línea Celular Tumoral , Humanos , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Ratones Endogámicos C57BL , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Apoptosis/efectos de los fármacos , Hierro/química , FemeninoRESUMEN
BACKGROUND: Polymeric microcapsules (MCs) have become an important issue and have attracted increasing attention because of their tunable physical and chemical properties. Diverse shell structures can confer multiple properties on MCs. RESULTS: Different polyols (1,4-butanediol and glycerin) and polyamines (triethylenetetramine and isophorondiamine) were selected as crosslinkers to obtain emamectin benzoate (EB)-loaded poly(urethane-urea) MCs (PU-MCs) by interfacial polymerization. The four obtained PU-MCs showed sphericity with different degrees of smoothness on their surfaces, and displayed a uniform size distribution ranging from 500 to 700 nm. Moreover, transmission electron microscopy showed that the shell thickness was roughly uniform, and was greatly influenced by the type and structure of the crosslinker. GI-MCs, prepared using glycerin and isophorondiamine, had the largest shell thickness. GT-MCs, obtained using glycerin and triethylenetetramine, had the highest encapsulation efficiency and drug-loading content, and BT-MCs, obtained using mixtures of 1,4-butanediol and triethylenetetramine, had the fastest release behavior. Thermogravimetric analysis revealed that the greater the degree of shell crosslinking, the higher decomposition temperature and the greater the thermal stability. A BT-MC suspension had the lowest viscosity and contact angle with the best wettability. Bioassay experiments showed that BT-MCs exhibited good insecticidal activity against Plutella xylostella larvae with a half-maximal lethal concentration of 4.19 mg/L. Furthermore, a BT-MC suspension showed good thermal and light stability, with potential applications in minimizing the toxicity of EB through sustained release. CONCLUSION: Various properties of EB-loaded PU-MCs were modulated through simple selection of different polyols and polyamines during fabrication, which might have an important role in constructing the pesticide delivery system and improving pesticide utilization. © 2024 Society of Chemical Industry.
Asunto(s)
Cápsulas , Animales , Poliuretanos/química , Polímeros/química , Mariposas Nocturnas/efectos de los fármacos , Insecticidas/farmacología , Insecticidas/química , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Reactivos de Enlaces Cruzados/química , Ivermectina/análogos & derivados , Ivermectina/química , Ivermectina/farmacologíaRESUMEN
A stepwise pretreatment of combination of bacterial treatment with NaOH/Urea (NU) treatment was conducted to enhance enzymatic hydrolysis of rice straw (RS). The results showed that the composition of RS changed significantly, the lignin and hemicellulose decreased while cellulose increased. The biological treatment with a bacterium Sphingobacterium sp. LD-1 achieved mild conditions for the sequential NU treatment, reducing the concentration of the NU solution from 7%/12% to 4%/6% and increasing the temperature from -20°C to -10°C. The saccharification of rice straw co-treated with bacterium Sphingobacterium sp. LD-1 and 4%/6% NU at -10°C resulted in 1.396-fold and 1.372-fold increase of reducing sugar and glucose yield respectively than that of sole NU treatment.