Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects in vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano‐bioconjugates for cancer therapy. Azide‐modified exosomes derived from M1 macrophages are conjugated with dibenzocyclooctyne‐modified antibodies of CD47 and SIRPα (aCD47 and aSIRPα) through pH‐sensitive linkers. After systemic administration, the nano‐bioconjugates can actively target tumors through the specific recognition between aCD47 and CD47 on the tumor cell surface. In the acidic tumor microenvironment, the benzoic‐imine bonds of the nano‐bioconjugates are cleaved to release aSIRPα and aCD47 that can, respectively, block SIRPα on macrophages and CD47, leading to abolished “don't eat me” signaling and improved phagocytosis of macrophages. Meanwhile, the native M1 exosomes effectively reprogram the macrophages from pro‐tumoral M2 to anti‐tumoral M1.
Soil disinfestation is an important agricultural practice to conquer soil-borne diseases and thereby ensure crop productivity. Reductive soil disinfestation (RSD) had been developed as an environmentally friendly alternative to chemical soil disinfestation (CSD). However, the differences between CSD and RSD on soil-borne pathogen suppression and fungal community structure remain poorly understood. In this work, five treatments, i.e., untreated soil (CK), CSD with 0.5 t ha dazomet (DZ), RSD with 10 t ha ethanol (ET), 15 t ha sugarcane bagasse (SB), and 15 t ha bean dregs (BD), were performed to investigate their influences on disinfestation efficiency, fungal abundance, diversity, and community structure via quantitative PCR and high-throughput sequencing. RSD-related treatments, especially the BD treatment, effectively alleviated soil acidification and salinization. The fungal abundance and microbial activity considerably increased in the BD treatment and significantly declined in the DZ treatment as compared to the CK treatment. Moreover, both CSD and RSD-related treatments significantly inhibited the population of Fusarium oxysporum and the relative abundance of genus Fusarium. Fungal community structure was notably altered by CSD and RSD practices. Furthermore, both CSD and RSD harbored a distinct unique microbiome, with the DZ treatment dominated by the genus Mortierella and BD treatment predominated by the genera Zopfiella, Chaetomium, and Penicillium. Taken together, these results indicate that the BD treatment could considerably alleviate the soil deterioration, improve soil microbial activity, and reassemble a non-pathogen unique microbiome that have more disease-suppressive agents and thus might be a promising disinfestation practice to control soil-borne disease in monoculture system.
Multifunctional nanomaterials for dual-mode imaging guided cancer therapy are highly desirable in clinical applications. Herein, a flowerlike NiS 2 -coated NaLuF 4 :Nd (Lu:Nd@NiS 2 ) nanoparticle was synthesized as a novel therapeutic agent for short-wave infrared light imaging and magnetic resonance imaging to guide photothermal therapy (PTT). The material was then loaded with phenolic epigallocatechin 3-gallate (EGCG), which is a natural heatshock protein 90 (HSP90) inhibitor. Upon near infrared irradiation, EGCG was released from the Lu:Nd@NiS 2 -EGCG, which bound HSP90 and reduced cell tolerance to heat, resulting in a better therapeutic effect at the same elevated temperature. Therefore, with minimal side effects and remarkable antitumor efficacy in vivo, Lu:Nd@NiS 2 -EGCG appeared to be a promising photothermal agent for enhanced PTT.
Nanoparticle emitting short-wave infrared (SWIR) light has received increased attention in the molecular imaging field due to its deeper tissue penetration, fast imaging, high sensitivity, and resolution. The simultaneously activated SWIR excited directly by an 808 nm laser and T 1 -weighted magnetic resonance imaging (MRI) signal are found in one single-shell nanoparticle NaErF 4 @NaGdF 4 (Er@Gd), which is used as a dual-modality imaging contrast agent in vivo to accurately determine the position of tumors. The conjugated cypate is then aggregated on the surface of Er@Gd@SiO 2 -Cy/bovine serum albumin. With the guidance of dual modality imaging, photothermal therapy is effectively used to ablate tumors in a mouse model. The design of single-shell nanomaterial activation of SWIR imaging and MRI signals is expected to provide a new strategy for high penetration and spatial resolution cancer theranostics.
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