Self-Cross-Linked Chitosan/Albumin-Bound Nanoparticle Hydrogel for Inhibition of Postsurgery Malignant Glioma Recurrence.

The development of chemoimmunotherapy with reduced systemic toxicity using local formulations is an effective strategy for combating tumor recurrence. Herein, we reported a localized hydrogel system for antitumor chemoimmunotherapy, formed by doxorubicin (DXR)-loaded bovine serum albumin (BSA) nanoparticles self-cross-linked with natural polysaccharide chitosan (CS). The drug-loaded hydrogel (DXR-CBGel) with antiswelling performance and prolonged drug-release profile was combined with antiprogrammed cell death protein 1 (aPD-1) as an in situ vaccine for treating glioblastoma multiforme (GBM) lesions. The antiswelling hydrogel system shows excellent biosafety for volume-sensitive GBM lesions. Both the albumin-bound formulation and the in situ gelation design facilitate the local retention and sustained release of DXR to generate long-term chemoimmunotherapy with reduced systemic toxicity. The chemotherapy-induced immunogenic cell death of DXR with the assistance of immunotherapeutic CS can trigger tumor-specific immune responses, which are further amplified by an immune checkpoint blockade to effectively inhibit cancer recurrence. The strategy of combining albumin-bound drug formulation and biocompatible polymer-based hydrogel for localized chemoimmunotherapy shows great potential against postsurgery glioblastoma recurrence.

Precisely Amplifying Intracellular Oxidative Storm by Metal-Organic Coordination Polymers to Augment Anticancer Immunity.

Oxidative stress accompanying the reactive oxygen species (ROS) burst governs immunocyte infiltration, activation, and differentiation in tumor microenvironments and thus can elicit robust antitumor immunity. Here, we identify a photoactive metal-organic coordination polymer (MOCP), composed of an organometallic core formed by cytotoxic mitoxantrone (MTX) acylates and photosensitive Ru(BIQ)-HDBB [BIQ = 2,2'-biquinoline, HDBB = 4,4'-di(4-benzoato)-2,2'-bipyridine] linked by Fe(II) ions via coordinate covalent bonds and an amphipathic shell encapsulating cholesterol-modified siRNA against GPX4 (siGPX4) via hydrophobic force, to precisely amplify intracellular oxidative storm. MOCPs simultaneously encapsulated MTX, Ru, and siGPX4 with efficiencies >98% and loaded Fe with efficiencies of ∼0.49%. With longer blood circulation and higher tumor accumulation, MOCPs with a 670 nm LED irradiation generate abundant ROS to induce biomembrane dysfunction and subsequently contribute to ferroptotic and immunogenic cell death, which drive tumor-associated antigen-specific immunity. MTX analogs contributed to Type I immunogenic cell death (ICD), while oxidative storm served as a damager for endo/lysosomal escape, an initiator for ferroptosis, and an inducer for type II ICD. Moreover, the blockade of CD73 that reduces extoATP catabolism unleashes immunosuppression, finally enhancing antitumor immune stimulation of MOCPs to promote orthotopic mammary cancer regression and prevent postoperative advanced cancer from recurrence and metastasis. MOCPs by exposing sufficient antigenicity thus provide a platform to synergize immune checkpoint inhibitors for the treatment of immunologically cold tumors.

Fabrication and Properties of the Multifunctional Rapid Wound Healing Panax notoginseng@Ag Electrospun Fiber Membrane.

The Panax notoginseng@Ag core/shell electrospun fiber membrane was prepared by coaxial electrospinning combined with the UV reduction method (254 nm). The prepared Panax notoginseng@Ag core/shell nanofiber membrane has a three-dimensional structure, and its swelling ratio could reach as high as 199.87%. Traditional Chinese medicine Panax notoginseng can reduce inflammation, and the silver nanoparticles have antibacterial effects, which synergistically promote rapid wound healing. The developed Panax notoginseng@Ag core/shell nanofiber membrane can effectively inhibit the growth of the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus. The wound healing experiments in Sprague Dawley mice showed that the wound residual area rate of the Panax notoginseng@Ag core/shell electrospun nanofiber membrane group was only 1.52% on day 9, and the wound of this group basically healed on day 12, while the wound residual area rate of the gauze treatment group (control group) was 16.3% and 10.80% on day 9 and day 12, respectively. The wound of the Panax notoginseng@Ag core/shell electrospun nanofiber membrane group healed faster, which contributed to the application of the nanofiber as Chinese medicine rapid wound healing dressings.

Age-Based Variations in the Gut Microbiome of the Shennongjia (Hubei) Golden Snub-Nosed Monkey (Rhinopithecus roxellana hubeiensis).

The gut microbiota represents a source of genetic and metabolic diversity of a complex polymicrobial ecosystem within its host. To investigate age-based variations of the gut microbiota among Shennongjia golden snub-nosed monkeys (Rhinopithecus roxellana hubeiensis), we characterized the microbial species in fecal samples from 18 Shennongjia golden snub-nosed monkeys evenly pooled into 3 aged groups (Group 1, 1-3 years; Group 2, 5-8 years; Group 3, above 12 years) in Shennongjia, Hubei Province, China. Genomic DNA was extracted from fecal samples, and the 16S rRNA gene V4 region was sequenced using the Illumina high-throughput MiSeq platform PE250. A total of 28 microbial phyla were identified in the gut microbiome of these monkeys with the ten most abundant phyla (i.e., Firmicutes, Bacteroidetes, Verrucomicrobia, Spirochaetes, Tenericutes, Proteobacteria, Planctomycetes, Fibrobacteres, Cyanobacteria, and Euryarchaeota). A total of 1,469 (of 16 phyla and 166 genera), 1,381 (of 16 phyla and 157 genera), and 1,931 (of 19 phyla and 190 genera) operational taxonomic units (OTUs) were revealed in Groups 1, 2, and 3, respectively, with Group 3 containing the most diverse groups of OTUs as revealed by the species relative abundance clustering analysis. These results suggest that the gut microbiota in these monkeys maintain a dynamic status, starting from the early developmental stages of life with the species relative abundance increasing with age. This is the first study to comprehensively characterize the gut microbiota and provide valuable information for monitoring the health and nutritional needs of this endangered primate at different ages.

Synthesis and modification of ZIF-8 and its application in drug delivery and tumor therapy.

Metal-organic frameworks have the properties of high porosity, variable pore sizes, and easy modification as drug delivery systems. In particular, ZIF-8 based on Zn2+ has been extensively studied in the medical field due to its low toxicity and good biocompatibility. This review introduces the preparation and functional modification of ZIF-8, and its application in drug delivery, focusing on the single-stimulus and multi-stimulus response release of drugs in ZIF-8 materials, the integrated role of diagnosis and treatment with ZIF-8 in cancer treatment, and its application in the synergistic therapy of multiple cancer treatment methods. We summarize the latest developments of ZIF-8 in the field of drug delivery and tumor therapy, and present the main challenges that remain to be resolved in the ZIF-8 drug delivery system.