Polyphenol-mediated assembly of toll-like receptor 7/8 agonist nanoparticles for effective tumor immunotherapy.

Toll-like receptor (TLR) 7/8 agonists have shown significant potential in tumor immunotherapy. However, the limited pharmacokinetic properties and systemic toxicity resulting from off-target effects limits their biomedical applications. We here report the polyphenol-mediated assembly of resiquimod (R848, a TLR7/8 agonist) nanoparticles (RTP NPs) to achieve tumor-selective immunotherapy while avoiding systemic adverse effects.

Amino Acid Metabolism-Regulated Nanomedicine for Enhanced Tumor Immunotherapy through Synergistic Regulation of Immune Microenvironment.

The reprogramming of tumor metabolism presents a substantial challenge for effective immunotherapy, playing a crucial role in developing an immunosuppressive microenvironment. In particular, the degradation of the amino acid L-tryptophan (Trp) to kynurenine (Kyn) by indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) is one of the most clinically validated pathways for immune suppression. Thus, regulating the Trp/Kyn metabolism by IDO1 inhibition represents a promising strategy for enhancing immunotherapy.

The two autophagy-related proteins 8a and 8b play distinct physiological roles in Drosophila.

Atg8 family proteins play crucial roles in autophagy to maintain cellular homeostasis. However, the physiological roles of Atg8 family proteins have not been systematically determined. In this study, we generated Atg8a and Atg8b (homologs of Atg8 in Drosophila melanogaster) knockout flies.

Hollow metal-organic framework-based, stimulator of interferon genes pathway-activating nanovaccines for tumor immunotherapy.

Nanovaccines have emerged as promising agents for cancer therapy because of their ability to induce specific immune responses without off-target effects. However, inadequate cytotoxic T lymphocyte response and low antigen/adjuvant encapsulation remain major obstacles to vaccinating against cancer. Herein, we designed a stimulator of interferon genes (STING) pathway-activating nanovaccine based on hollow metal-organic frameworks (MOFs) for tumor treatment.

Vaccination of TLR7/8 Agonist-Conjugated Antigen Nanoparticles for Cancer Immunotherapy.

Nanovaccine-based immunotherapy can initiate strong immune responses and establish a long-term immune memory to prevent tumor invasion and recurrence. Herein, the assembly of redox-responsive antigen nanoparticles (NPs) conjugated with imidazoquinoline-based TLR7/8 agonists for lymph node-targeted immune activation is reported, which can potentiate tumor therapy and prevention. Antigen NPs are assembled via the templating of zeolitic imidazolate framework-8 NPs to cross-link ovalbumin with disulfide bonds, which enables the NPs with redox-responsiveness for improved antigen cross-presentation and dendritic cell activation.

Enhanced Delivery of TLR7/8 Agonists by Metal-Organic Frameworks for Hepatitis B Virus Cure.

Hepatitis B virus (HBV) infection remains a major challenge to global health due to unsatisfactory treatment efficacy, side effects of current therapies, and immune tolerance. Toll-like receptors 7/8 (TLR7/8) agonists have shown great potential in chronic hepatitis B (CHB) cure, but systemic administration often induces severe side effects due to rapid dispersion into the microvasculature. Herein, we encapsulate an imidazoquinoline-based TLR7/8 agonist (IMDQ) into zeolitic imidazolate framework 8 nanoparticles (IMDQ@ZIF-8 NPs) for HBV immunotherapy.

Bimetallic metal-organic frameworks for tumor inhibition combined photothermal-immunotherapy.

Herein, we report the design of therapeutic nanoparticles by encapsulating photosensitizers and aluminum ions into metal-organic frameworks. The nanoparticles could significantly inhibit the growth of primary and rechallenged tumors by a combination of photothermal therapy and immunotherapy. This work offers a promising strategy to design an immunologic nanoplatform for "cold" tumor therapy.

Self-adjuvanting photosensitizer nanoparticles for combination photodynamic immunotherapy.

Combination cancer immunotherapy that synergizes the advantages of multiple therapeutic agents has shown great potential in tumor treatment. Herein, we report the one-step assembly of therapeutic nanoparticles (NPs) to co-deliver photosensitizers and adjuvants for combination photodynamic therapy (PDT) and immunotherapy. The NPs are obtained self-assembly of chlorin e6 (Ce6) and imidazoquinoline-based TLR7 agonists (IMDQ), which results in a high loading efficacy of 72.

Poly(ethylene glycol)-Mediated Assembly of Vaccine Particles to Improve Stability and Immunogenicity.

We report the one-step assembly of vaccine particles by encapsulating ovalbumin (OVA) and cytosine-phosphate-guanine oligodeoxynucleotides (CpG) into poly(ethylene glycol) (PEG)-mediated zeolitic imidazolate framework-8 nanoparticles (OVA-CpG@ZIF-8 NPs), where PEG improves the stability and dispersity of ZIF-8 NPs and the NPs protect the encapsulated OVA and CpG to circumvent the cold chain issue. Compared with free OVA and OVA-encapsulated ZIF-8 (OVA@ZIF-8) NPs, OVA-CpG@ZIF-8 NPs can enhance antigen uptake, cross-presentation, dendritic cell (DC) maturation, production of specific antibody and cytokines, and CD4 T and CD8 T cell activation. More importantly, the vaccine particles retain their bioactivity against enzymatic degradation, elevated temperatures, and long-term storage at ambient temperature.

Poly(ethylene glycol)-mediated mineralization of metal-organic frameworks.

We report a one-pot approach for the scalable synthesis of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) using poly(ethylene glycol) as the mineralizer, where drugs and proteins can be encapsulated in the ZIF-8 NPs for intracellular delivery. The ZIF-8 NPs exhibit high colloidal dispersity and stability (above two weeks) in cell medium.

Upregulation of EID3 sensitizes breast cancer cells to ionizing radiation-induced cellular senescence.

Previous studies have shown that BMS-345541 (BMS, a specific IκB kinase β inhibitor) sensitized various tumor cells including MCF-7 breast cancer cells to ionizing radiation (IR). However, the mechanisms of BMS action are unknown. Since the expression of E1A-like inhibitor of differentiation 3 (EID3) was highly upregulated in MCF-7 cells after BMS treatment, we investigated the role of EID3 in the response of MCF-7 cells to IR.

Conjugation of chitosan oligosaccharides via a carrier protein markedly improves immunogenicity of porcine circovirus vaccine.

Porcine circovirus type 2 (PCV2)-associated diseases have led to huge economic losses in pig industry. Our laboratory previously found that conjugation of chitosan oligosaccharides (COS) enhanced the immunogenicity of PCV2 vaccine against infectious pathogens. In this study, an effective adjuvant system was developed by covalent conjugation of COS via a carrier protein (Ovalbumin, OVA) to further increase the immunogenicity of vaccine.

Conjugation of chitosan oligosaccharides enhances immune response to porcine circovirus vaccine by activating macrophages.

Porcine circovirus type 2 (PCV2)-associated diseases have led to great economic losses to the pig industry. Our lab previously found that conjugation of chitosan oligosaccharides (COS) or via a carrier protein enhanced the immunogenicity of PCV2 vaccine against infectious pathogens. However, precise mechanisms and signal transduction pathways underlying the efficacy of COS conjugation remains poorly defined.

Conjugation of Inulin Improves Anti-Biofilm Activity of Chitosan.

Bacteria biofilm helps bacteria prevent phagocytosis during infection and increase resistance to antibiotics. is a Gram-positive pathogenic bacterium and is tightly associated with biofilm-related infections, which have led to great threat to human health. Chitosan, the only cationic polysaccharide in nature, has been demonstrated to have antimicrobial and anti-biofilm activities, which, however, require a relative high dosage of chitosan.

Correction: Zhang, G.; Cheng, G.; Jia, P.; Jiao, S.; Feng, C.; Hu, T.; Liu, H.; Du, Y. The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree. Marine Drugs 2017, 15, 236.

The authors wish to correct Figure 1 in this paper [1] to be as follows:[...

The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree.

Chitosan oligosaccharides (COS), the degraded products of chitosan, have been demonstrated to have versatile biological functions. In primary studies, it has displayed significant adjuvant effects when mixed with other vaccines. In this study, chitosan oligosaccharides with different deacetylation degrees were prepared and conjugated to porcine circovirus type 2 (PCV2) subunit vaccine to enhance its immunogenicity.

Enhanced immune response to inactivated porcine circovirus type 2 (PCV2) vaccine by conjugation of chitosan oligosaccharides.

This study aimed to investigate the effect of chitosan oligosaccharide (COS) conjugation on the immunogenicity of porcine circovirus type-2 (PCV2) vaccine. Two conjugates (PCV2-COS-1 and PCV2-COS-2) were designed by covalent conjugation of an inactivated PCV2 vaccine with COS, and administered to C57BL/6 mice three times at two-week intervals. The results indicate that, as compared to PCV2 alone group, the PCV2-COS conjugates remarkably enhanced both humoral and cellular immunity against PCV2 by promoting T lymphocyte proliferation and initiating a mixed Th1/Th2 response, including the elevated production of PCV-2 specific antibodies and up-regulated secretion of inflammatory cytokines.

A novel antisense long non-coding RNA SATB2-AS1 overexpresses in osteosarcoma and increases cell proliferation and growth.

The knowledge regarding the importance of long non-coding RNAs (lncRNAs), a new class of genes, is very sparse in osteosarcoma. In the present study, we describe the expression profile of lncRNAs in osteosarcomas compared with paired adjacent non-cancerous tissue (n = 7) using microarray analysis. A total of 25,733 lncRNAs were identified in osteosarcoma; 1995 lncRNAs were consistently upregulated and 2226 lncRNAs were consistently under-regulated in all samples analyzed (≥2.

Anticancer effect of thalidomide in vitro on human osteosarcoma cells.

Osteosarcoma is a high‑grade malignant tumor frequently found in children and adolescents. Thalidomide has been reported for treatment of various malignancies. Thalidomide was added to osteosarcoma cells and studied by cytotoxicity assay, evaluating apoptosis, cell cycle arrest, mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) levels and the expression of Bcl‑2, Bax, caspase‑3 and NF‑κB.

Anticancer Activity Studies of Ruthenium(II) Complex Toward Human Osteosarcoma HOS Cells.

A new Ru(II) complex [Ru(dmp)2(NMIP)](ClO4)2 (dmp = 2,9-dimethyl-1,10-phenanthroline, NMIP = 2'-(2″-nitro-3″,4″-methylenedioxyphenyl)imidazo[4',5'-f][1,10]-phenanthroline) was synthesized and characterized by elemental analysis, ESI-MS and (1)H NMR. The cytotoxic activity of the complex against MG-63, U2OS, HOS, and MC3T3-e1 cell lines was investigated by MTT method. The complex shows moderate cytotoxicity toward HOS (IC50 = 35.

Protein-binding, cytotoxicity in vitro and cell cycle arrest of ruthenium(II) polypyridyl complexes.

The cytotoxic activity of two Ru(II) complexes against A549, BEL-7402, HeLa, PC-12, SGC-7901 and SiHa cell lines was investigated by MTT method. Complexes 1 and 2 show moderate cytotoxicity toward BEL-7402 cells with an IC50 value of 53.9 ± 3.