Inflammatory bowel disease (IBD) is an incurable disease of the digestive system; however, the therapeutic methods for IBD remain limited. The pathogenesis of IBD was systematically discussed and compared in this paper, primarily comprising Crohn’s disease and ulcerative colitis. This paper focused on six common aspects: (1) Dysregulated immune responses; (2) Gene function changes; (3) Intestinal microbes disorder and imbalance; (4) Microbial infections; (5) Associations between IBD and other inflammatory diseases; and (6) Other factors. In addition, the pathogenesis differences between these two forms of IBD were unraveled and clearly distinguished. These unique aspects of pathogenesis provide crucial insights for the precise treatment of both Crohn’s disease and ulcerative colitis. This paper illustrates the root causes and beneficial factors of resistance to IBD, which provides novel insights on early prevention, development of new therapeutic agents, and treatment options of this disease.
Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy. Herein, a pH-responsive gold nanoassembly is designed to overcome these problems. Polyethylene glycol linked raltitrexed (RTX, target ligand and chemotherapy drug) and two tertiary amine molecules (1-(2-aminoethyl) pyrrolidine and N, N-dibutylethylenediamine) are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX). The Au-NNP (RTX) nanoassembly could remain at about 160 nm at the blood circulation (pH 7.4), while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH (pH 6.8). This pH-responsive disassembly behavior endows Au-NNP(RTX) better tumor tissue permeability through the better diffusion brought by the size reduction. Meanwhile, after disassembly, more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability. Most importantly, the results show that Au-NNP(RTX) possesses of high tumor accumulation and effective tumor penetration, thereby enhancing the tumor chemo-radiotherapy efficiency.
Liver cancer is the most common malignant tumor and liver cancer immunotherapy has been one of the research hotspots. To induce antigen-specific antitumor immune responses against liver cancer, we developed antigen and adjuvant co-delivery nanovaccines (APPCs). Polyanionic alginate (ALG) and polycationic polyethyleneimine (PEI) were utilized to co-deliver a glypican-3 peptide antigen and an unmethylated cytosine-phosphate-guanine (CpG) adjuvant by electrostatic interactions. A cellular uptake study confirmed that APPC could promote antigen and adjuvant uptake by dendritic cells (DCs). Importantly, APPC facilitated the endosomal escape of the peptide for antigen delivery into the cytoplasm. In addition, APPC showed significant stimulation of DC maturation in vitro. APPC could also efficiently prime DCs and induce cytotoxic T lymphocyte responses in vivo. The in vitro cell viability assay and the in vivo histocompatibility showed that APPC was non-toxic within the tested concentration. This study demonstrates that the peptide antigen and the CpG adjuvant co-delivery nanovaccine have potential applications in liver cancer immunotherapy.