Surface charge plays an important role in determining the interactions of nanoparticles with biological components. Substantial studies have demonstrated that surface charge affects the fate of nanoparticles after intravenous administration; however, few studies have investigated the effect of surface charge on the bioavailability and absorption of nanoparticles after oral administration. In this study, polymeric nanoparticles with a similar particle size and surface polyethylene glycol (PEG) density, but with varying surface charges (positive, negative and neutral), were developed to study the effect of surface charge on the oral absorption of polymeric nanoparticles. The nanoparticles were constructed from polyethylene glycol-block-polylactic acid (PEG-PLA) with the incorporation of lipid components with different charges. Our results suggested that the positive surface charge facilitated the cellular uptake and transport of nanoparticles through both Caco-2 cells in vitro and small intestinal epithelial cells in vivo. The positively charged nanoparticles showed a favorable distribution in the small intestine, and significantly improved the oral bioavailability. This study presents valuable information towards the design of nanoparticles for improved oral drug delivery.

As one of the significant challenges to human health, cancer has long been a focal point in medical treatment. With ongoing advancements in the field of medicine, numerous methodologies for cancer therapy have emerged, among which oncolytic virus therapy has gained considerable attention. However, oncolytic viruses still exhibit limitations. Combining them with various therapies can further enhance the efficacy of cancer treatment, offering renewed hope for patients. In recent research, scientists have recognized the promising prospect of amalgamating oncolytic virus therapy with diverse treatments, potentially surmounting the restrictions of singular approaches. The central concept of this combined therapy revolves around leveraging oncolytic virus to incite localized tumor inflammation, augmenting the immune response for immunotherapeutic efficacy. Through this approach, the patient's immune system can better recognize and eliminate cancer cells, simultaneously reducing tumor evasion mechanisms against the immune system. This review delves deeply into the latest research progress concerning the integration of oncolytic virus with diverse treatments and its role in various types of cancer therapy. We aim to analyze the mechanisms, advantages, potential challenges, and future research directions of this combination therapy. By extensively exploring this field, we aim to instill renewed hope in the fight against cancer.

Background: Ulcerative colitis (UC) is a major type of inflammatory bowel disease (IBD), which could induce bloody stool, diarrhea, colon atrophy and eventually lead to colorectal cancer. The conventional daily oral administration of drugs only relieve the inflammatory response of colon in the short term, Biological agents such as antibody drugs has proven its efficiency in inhibiting colitis, while the low drug bioavailability means that large doses of antibodies are required, ultimately causing systemic toxicity. Small interfering RNA (siRNA) has significant advantages over antibody drugs in terms of safety and efficacy, and it have been widely applied as potential candidates for a variety of inflammation-related diseases. However, oral delivery of siRNA fails to overcome the degradation of the gastrointestinal environment to produce a significant therapeutic effect in ulcerative colitis. Herein, we design the hybrid delivery system that the siRNA loaded MOF encapsulated in the sodium alginate particles to overcome the barriers in the oral process. Results: The hybrid delivery system (SA@MOF-siRNA^TNFα) was successfully constructed, and it could not only survive the low pH environment in the stomach and small intestine, but also taken up more by inflammatory macrophages, as well as released much more MOF-siRNA^TNFα. Moreover, SA@MOF-siRNA^TNFα tended to enriched and infiltrated into local colon tissues. As a result, SA@MOF-siRNA^TNFα significantly reduced the progression of colitis, of which the treated mice did not experience significant weight loss, bloody stools and diarrhea. Conclusion: We confirmed that the formulation of hydrogel–metal-organic framework hybrids could improve the protection of incorporated payload in the gastric and early small intestine, enhancing the delivery of MOF-siRNA to colon.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.