An Antioxidative and Active Shrinkage Hydrogel Integratedly Promotes Re-Epithelization and Skin Constriction for Enhancing Wound Closure.

Delayed re-epithelization and weakened skin contractions are the two primary factors that hinder wound closure in large-scale acute or chronic wounds. However, effective strategies for targeting these two aspects concurrently are still lacking. Herein, an antioxidative active-shrinkage hydrogel (AHF@AS Gel) is constructed that can integratedly promote re-epithelization and skin constriction to accelerate large-scale acute and diabetic chronic wound closure. The AHF@AS Gel is encapsulated by antioxidative amino- and hydroxyl-modified C70 fullerene (AHF) and a thermosensitive active shrinkage hydrogel (AS Gel). Specifically, AHF relieves overactivated inflammation, prevents cellular apoptosis, and promotes fibroblast migration in vitro by reducing excessive reactive oxygen species (ROS). Notably, the AHF@AS Gel achieved ≈2.7-fold and ≈1.7-fold better re-epithelization in acute wounds and chronic diabetic wounds, respectively, significantly contributing to the promotion of wound closure. Using proteomic profiling and mechanistic studies, it is identified that the AHF@AS Gel efficiently promoted the transition of the inflammatory and proliferative phases to the remodeling phase. Notably, it is demonstrated that AS Gel alone activates the mechanosensitive epidermal growth factor receptor/Akt (EGFR/Akt) pathway and promotes cell proliferation. The antioxidative active shrinkage hydrogel offers a comprehensive strategy for acute wound and diabetic chronic wound closure via biochemistry regulation integrating with mechanical forces stimulation.

Oral fullerene tablets for colorectal cancer therapy based on modulation of tumor inflammatory microenvironments.

The development and progression of colorectal cancer (CRC) are highly dependent on the long-term inflammatory microenvironment with immune dysregulation in the colorectum. However, effective therapeutics are limited to targeting CRC. Here, we developed oral fullerene tablets (OFTs) that can act directly on the colorectal site by oral administration and reduce the inflammatory state at the tumor site for effective CRC therapy. In detail, OFTs scavenged reactive oxygen species (ROS), restrained the mutation of the wild-type P53, inhibited the activation of the inflammatory pathway nuclear factor-κB (NF-κB) and the signal transducer and activator of transcription 3 (STAT3) in the colorectum of CRC mice. Subsequently, OFTs could greatly reduce the infiltration of pro-inflammatory M1 macrophages and neutrophils at the tumor site, restoring the inflammatory microenvironment and immune homeostasis in the colorectal region, and ultimately achieving the inhibition of CRC. In addition, there were no significant toxic side effects of the long-term administration of OFTs. Our work provides an effective oral therapeutic strategy for CRC therapy by modulating the colorectal tumor inflammatory microenvironment and sheds light on the route for oral nano-materials in the clinical treatment of CRC.

Fullerene nanoparticles for the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a long-term, recurrent inflammatory bowel disease for which no effective cure is yet available in the clinical setting. Repairing the barrier dysfunction of the colon and reducing intestinal inflammation are considered key objectives to cure UC. Here we demonstrate a novel therapeutic strategy based on a C60 fullerene suspension (C60FS) to treat dinitrobenzene sulfonic acid-induced UC in an animal model. C60FS can repair the barrier dysfunction of UC and effectively promote the healing of ulcers; it also manifests better treatment effects compared with mesalazine enema. C60FS can reduce the numbers of basophils in the blood of UC rats and mast cells in the colorectal tissue, thereby effectively alleviating inflammation. The expression of H1R, H4R, and VEGFR2 receptors in colorectal tissues is inhibited by C60FS, and the levels of histamine and prostaglandin in the rat blood are reduced. This work presents a reliable strategy based on fullerene to cure UC and provides a novel guide for UC treatment.

A gadofullerene based liver-specific MRI contrast agent for an early diagnosis of orthotopic hepatocellular carcinoma.

Hepatocellular carcinoma has become one of the most prevalent cancers, with a high mortality rate. Accurate diagnosis at an earlier stage is regarded as an effective measure to reduce the disease-related mortality of liver cancer. Magnetic resonance imaging (MRI) as a non-invasive checking mode has become a powerful tool in medical diagnosis. However, MRI contrast agents for liver-specific imaging either have some side effects or the imaging effect is not ideal. Thus, development of more efficient and security MRI contrast agents for the early diagnosis of hepatocellular carcinoma is urgent. Herein, a kind of water-soluble gadofullerene nanoparticle (GFNP) with high efficiency and security has been successfully used to achieve in situ liver cancer imaging. By comparing GFNPs with different functional groups, Gd@C82 modified by a hydroxyl group (GF-OH) presents the highest contrast efficiency both in vitro and in vivo. Notably, the smallest tumor with a diameter of only 0.5 mm could be clearly observed by GF-OH using MRI. Moreover, the imaging window of GF-OH is more than 3-6 hours. In addition, GF-OH can be mostly excreted from the living body and causes no serious toxicity. These results demonstrate that GF-OH is a safe, efficient MRI contrast agent for the diagnosis of early orthotopic hepatocellular carcinoma.