Background Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed. Results For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (− 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis. Conclusion Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown etiology affecting the colon and rectum. Previous studies have found that reactive oxygen species (ROS) overproduction and transmembrane glycoprotein CD98 (encoded by SLC3A2) upregulation played important roles in the initiation and progression of UC. On the basis of this, a biomimetic pH-responsive metal organic framework (MOF) carrier was constructed to deliver carbon nanodot-SOD nanozyme and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) system for site-specific treatment of UC. In this system, carbon nanodots (C-dots) and CD98 CRISPR/Cas9 plasmid were successfully encapsulated into MOF carrier (ZIF-8 nanoparticles) by a one-pot approach (formed as CCZ), and then camouflaged with macrophage membrane (formed as CCZM). It was worth noting that the C-dot nanozyme showed excellent superoxide dismutase (SOD) enzymatic activity, which could scavenge ROS effectively. As expected, this biomimetic system exhibited pH-responsive, immune escape, and inflammation targeting capability simultaneously. In vitro experiments showed that ROS was significantly eliminated, and CD98 was downregulated by CCZM. In the dextran sulfate sodium salt (DSS)-induced UC model, administration of CCZM significantly ameliorated the inflammation symptoms of mice, including the colon length and pathological parameters such as epithelium integrity and inflammation infiltration. In addition, both in vitro and in vivo results demonstrated that biomimetic nanoparticles effectively reduced the expression of pro-inflammatory cytokines. Overall, this study would provide a promising approach for the precise treatment of UC.

Background Inflammatory bowel disease (IBD) is a chronic nonspecific disease with unknown etiology. Currently, the anti-inflammatory therapeutic approaches have achieved a certain extent of effects in terms of inflammation alleviation. Still, the final pathological outcome of intestinal fibrosis has not been effectively improved yet. Results In this study, dextran-coated cerium oxide (D-CeO2) nanozyme with superoxide dismutase (SOD) and catalase (CAT) activities was synthesized by chemical precipitation. Our results showed that D-CeO2 could efficiently scavenge reactive oxide species (ROS) as well as downregulate the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and iNOS) to protect cells from H2O2-induced oxidative damage. Moreover, D-CeO2 could suppress the expression of fibrosis-related gene levels, such as α-SMA, and Collagen 1/3, demonstrating the anti-fibrotic effect. In both TBNS- and DSS-induced colitis models, oral administration of D-CeO2 in chitosan/alginate hydrogel alleviated intestinal inflammation, reduced colonic damage by scavenging ROS, and decreased inflammatory factor levels. Notably, our findings also suggested that D-CeO2 reduced fibrosis-related cytokine levels, predicting a contribution to alleviating colonic fibrosis. Meanwhile, D-CeO2 could also be employed as a CT contrast agent for noninvasive gastrointestinal tract (GIT) imaging. Conclusion We introduced cerium oxide nanozyme as a novel therapeutic approach with computed tomography (CT)-guided anti-inflammatory and anti-fibrotic therapy for the management of IBD. Collectively, without appreciable systemic toxicity, D-CeO2 held the promise of integrated applications for diagnosis and therapy, pioneering the exploration of nanozymes with ROS scavenging capacity in the anti-fibrotic treatment of IBD.

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that features colonic epithelial barrier dysfunction and gut dysbiosis. Preclinical studies demonstrated that inhibiting the overexpression of CD98 via small...

Inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing disorders of the gastrointestinal tract. Characterized pathologically by intestinal inflammation and epithelial injury, great challenges exist for the treatment of IBD due to its complicated etiology and incurable nature. Traditional strategies rely on frequent and long-term administration of high dosages of anti-inflammatory drugs, which inevitably cause side effects. Therefore, novel therapeutic methods and drug delivery systems capable of improving therapeutic effect while simultaneously decreasing side effects need to be developed. The emergence of nanotechnology provides alternative approaches for diagnosis and treatment of IBD, as nanoparticles (NPs) have unique physicochemical properties such as targeting to the site of inflammation and the ability to alter the pharmacokinetics of traditional drugs. This review first introduces the pathophysiological features and microenvironment of IBD, and then summarizes different strategies and mechanisms of NP-based colon-targeted drug delivery systems, including size-dependent, multi-stimuli responsive, active targeting, intestinal microbiota-related, and novel natural-derived NP-mediated drug delivery systems. We also discuss applications of nanozymes and NP-based imaging in diagnostics and treatment of IBD. Finally, challenges and prospects in the field are proposed to promote the development of targeted drug delivery for IBD treatment.

A biocompatible natural nanoparticle drug delivery system that has specific cancer-targeting function holds vast promise for cancer therapy. Here, a fucoidan/poly-lysine-functionalized layer-by-layer ginger-derived lipid vector (LbL-GDLV) is designed to target P-selectin and deliver a loaded drug into vascularized colon cancer. LbL-GDLVs selectively bound to P-selectin, and the degradation of the fucoidan result in rapid attachment of the cancer cell and internalization of the remaining positively charged poly-lysine coated-GDLVs. Upon enzymolysis of the poly-lysine layer inside the cancer cell, the GDLV core releases loaded doxorubicin (Dox) which has the expected effects. Bio-distribution studies show that intravenously injected LbL-GDLVs exhibit enhanced accumulation at the vascularized tumor site (≈4.4-fold higher than control), presumably due to P-selectin-mediated targeting plus the enhanced permeability and retention effect (EPR). In two animal models (Luc-HT-29 and HCT-116 xenografts), Dox-loaded LbL-GDLVs (LbL-GDLVs/Dox) significantly inhibit tumor growth and demonstrate much better therapeutic efficiency than free Dox. More importantly, LbL-GDLVs exhibit excellent biocompatibility, and LbL-GDLVs encapsulation largely reduces the cardiotoxicity of free Dox and avoids the notorious drug resistance of colon cells against free Dox. Together, these findings demonstrate the potential of our newly designed and highly biocompatible plant-derived LbL nanoparticles and their precise colon cancer drug delivery function.

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Background Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), has evolved into a global burden given its high incidence. There is a clinical need to create better diagnostic and therapeutic approaches to UC. Results We fabricated P-selectin binding peptide-decorated poly lactic-co-glycolic acid (PBP-PLGA-NP) doped with two lipophilic dyes, DiL and DiD. Meanwhile, two low-toxic anti-inflammatory natural products (betulinic acid [BA] and resveratrol [Res]) were co-loaded in the PBP-PLGA-NP system. The BA/Res-loaded NPs had an average size of around 164.18 nm with a negative zeta potential (− 25.46 mV). Entrapment efficiencies of BA and Res were 74.54% and 52.33%, respectively, and presented a sustained drug release profile. Further, the resulting PBP-PLGA-NP could be internalized by RAW 264.7 cells and Colon-26 cells efficiently in vitro and preferentially localized to the inflamed colon. When intravenously injected with luminol, MPO-dependent bioluminescence imaging to visualize tissue inflammation was activated by the bioluminescence and fluorescence resonance energy transfer (BRET-FRET) effect. Importantly, injected NPs could remarkably alleviate UC symptoms yet maintain intestinal microbiota homeostasis without inducing organ injuries in the mice models of colitis. Conclusions This theranostic nano-platform not only serves as a therapeutic system for UC but also as a non-invasive and highly-sensitive approach for accurately visualizing inflammation. Graphical Abstract