Luciferase Reporter Cell Line - MGC803

Intraperitoneal chemotherapy (IPC) is considered an effective treatment for advanced gastric cancer (GC), especially for patients with peritoneal metastases. However, its limited efficacy, complications caused by chemotherapy drugs, and the need for repeated infusions restrict the application of IPC. Here, researchers constructed a biocompatible and biodegradable nanocomposite consisting of smart gelatin enzyme-responsive nanoparticles (NPs) and a thermosensitive gel, wherein the nanoparticles are prepared from polyethylene glycol-polycaprolactone (PEG-PCL) in different proportions. The researchers co-loaded the cancer stem cell (CSC) inhibitor thalinomycin (SAL) and the non-CSC inhibitor docetaxel (DOC) into the nanoparticles and delivered the drugs via a room-temperature liquid PEG-PCL-PEG gel (PECE). This PECE can target tumors and form a gel in situ at body temperature. Compared with the same dose of free SAL-DOC solution, the PECE NP group showed a more significant inhibitory effect on the growth of intraperitoneal metastatic gastric cancer, with some patients even achieving complete remission (CR), and the efficacy lasting for more than 2 weeks. Flow cytometry analysis of abdominal tumor tissue cell suspensions showed that the PECE NP group had the lowest proportion of cancer stem cells (CSC, CD44+CD133+) and the lowest expression of PD-L1 on tumor cells. In a mouse model of gastric cancer allogeneic transplantation, PECE NP significantly promoted the infiltration of M1 macrophages into the tumor bed. This design holds promise for providing a biodegradable, intelligent drug delivery system for intraperitoneal metastatic gastric cancer (IPC).

Here, researchers tested the effectiveness of intraperitoneal injection therapy in animal models. Luciferase-expressing MGC803 cells (MGC803-luc) were intraperitoneally injected into Balb/c nude mice. Two weeks later, mice with different tumor burdens were randomly divided into six groups, receiving intraperitoneal injections of PBS, blank PECE nanoparticles, free SAL-DOC, PECE/free SAL-DOC nanoparticles, and PECE nanoparticles, respectively. Nude mice carrying MGC803-luc tumors in the peritoneum were evaluated using a non-invasive in vivo imaging system. The tumor burden in the blank group was significantly increased, consistent with the results in the PBS group (Figure 1a). Both free SAL-DOC and PECE/free SAL-DOC effectively inhibited tumor growth, indicating that the combination of intraperitoneal injection of SAL-DOC has an in vivo antitumor effect (Figure 1c). However, metastatic tumors were not completely eliminated, regrowing after initial regression in the first 1-2 weeks (Figure 1c). This is likely because SAL and DOC, being lipid-soluble drugs, are difficult to distribute within the extracellular matrix (ECM), and therefore rarely diffuse to all tumor cells.

Figure 1. In vivo antitumor effect. (Wang X, et al., 2022)