Photoimmunotherapy (PIT) employs photosensitizers that generate reactive oxygen species (ROS) under near-infrared laser irradiation to induce immunogenic cell death (ICD) and trigger systemic antitumor immunity. However, the hypoxic conditions within tumors markedly reduce photosensitization efficiency and therapeutic efficacy. Moreover, insufficient immune activation together with the profoundly suppressive tumor immune microenvironment further compromises treatment outcomes. Given these challenges, it is imperative to develop an integrated therapeutic platform capable of effectively overcoming these limitations. Here, a responsive delivery system has been developed that utilizes ROS and incorporates the immunomodulatory agent Astragalus polysaccharide (APS). Hydrophobic rapamycin (RAPA) is linked to the APS backbone through an ROS-sensitive thioether TK bond, forming the amphiphilic APS-TK-RAPA (ATKR) conjugate. Subsequently, the photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) is integrated into the system. The designed ATKR conjugate carrier facilitates the maturation of dendritic cells (DCs), effectively captures antigens released during PDT, and enhances antigen presentation. This further amplifies the adaptive immune response mediated by the APS-based carrier, thereby strengthening antitumor efficacy. In summary, ATKR with superior biocompatibility effectively surmounts the delivery challenges of hydrophobic photosensitizers. Moreover, it offers a promising nanoscale platform to address the critical issue of hypoxia in photodynamic therapy for cancer, serving as an effective inducer for augmenting immune responses.
- Article type
- Year
- Co-author
Open Access
Research Article
Issue
Open Access
Article
Issue
Colorectal cancer (CRC) is one of the most common cancers all over the world. The progression of CRC is associated with inflammation and disruptions in intestinal flora. 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) has been noted for its potent anti-inflammatory properties. However, the effect of AKBA on colon cancer caused by inflammation and its mechanism are not unclear. The study is to explore the effect of AKBA on CRC and its mechanism.
Cell proliferation, (5-ethynyl-2′-deoxyuridine, EdU)-DNA synthesis assay and colony formation were used to assess the effect of AKBA on the proliferation of CRC cells. Flow cytometry was employed to analyze the cell cycle and apoptosis rate of cells treated with AKBA. RNA sequencing was done to explore the underlying mechanisms of AKBA. Western blot was used to assess the expression of key proteins in the nuclear factor kappa-B (NF-κB) signaling pathway after the treatment of AKBA. Real-time quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Meso Scale Discovery (MSD) assays were employed to check the anti-inflammation effects of AKBA on Lipopolysaccharide (LPS)-induced RAW264.7 cells and LPS-induced mouse model. Additionally, the Azoxymethane/Dextran sulfate sodium (AOM/DSS)-induced colitis-associated CRC model was used to evaluate the anti-CRC effect of AKBA. Gut microbiota profiling of fecal samples from CRC mice, both with and without AKBA treatment, was conducted through metagenomic sequencing analysis.
Our results showed that AKBA reduced the proliferation of HCT116 and SW620 cells, increased apoptosis of cells, and arrested the cell cycle at the G2/M phase. Results from RNA-seq showed that AKBA inhibited CRC by inhibiting the NF-κB signaling pathway and reducing cellular inflammation. Furthermore, AKBA reduced the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), Interleukin-IL-12p70 (IL-12p70), Interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in both the spleen and serum of LPS-induced acute inflammation mice. Additionally, AKBA inhibited the development of AOM/DSS-induced colitis-associated colon cancer in mice and positively influenced gut microbiota.
This study highlights the inhibitory effect of AKBA on colitis-associated CRC and reveals a novel aspect of its role in the remodeling of gut microbiota. These findings suggest that AKBA may be used as a potential therapeutic agent for CRC.
Open Access
Review Article
Issue
The emergence of meal replacement (MR) originates from physical exercise or fitness as a substitute for one or all meals and later expands to the field of weight loss. Indeed, the main application of current meal replacement is to lose body weight, whether patients with obesity, diabetes, fatty liver, infertile or pregnant women can benefit from weight loss. In addition, MRs still exhibit more biomedical potential in preventing and treating diseases, like anti-diabetes, improving fatty liver and kidney disease, preventing cancer, conceiving and reducing pregnancy complications, and improving life quality. Indeed, there are also disadvantages to meal replacement, including causing adverse effects, although most are acceptable and tolerated. To date, various commercially-developed MRs are walking from dining table to sickbed. Therefore, a scientific understanding of the advantages and disadvantages of meal replacements is crucial for their extensive application beyond biomedical potentials.
京公网安备11010802044758号