Page 86 - ARNM-3-3

Advances in Radiotherapy
& Nuclear Medicine CS@LGG for acute radiation-induced bowel injury alleviation

greatly restored lesions in the intestinal tract compared demonstrates that CS@LGG treatment protected normal
with the sham group or single-material treatment groups. cells from IR without promoting tumor growth.
Specifically, the biomaterial-treated group exhibited To further explore the in-depth mechanism of the CS@
aligned villi, intact crypts, and a normal villi-to-crypt ratio. LGG curative effect, we conducted whole transcriptome
Moreover, it raised the levels of CLDN3 and OCCLDN in sequencing. The differential genes and their expressions
the intestinal tract, as shown in Figure 3E, H, and I. These between the three treatments are displayed in Figure 6A-C.
are key tight junction proteins essential for maintaining Furthermore, we attempted to identify the specific
intestinal permeability. In addition, the FITC-labeled functional pathways and related genes. Thus, we performed
dextran assay (Figure 3G) showed that fluorescence GO term analysis for biological processes, molecular
intensity was the lowest after 3 days of biomaterial gavage, functions, and cellular components (Figure 6D-F).
indicating recovery of the intestinal barrier from radiation-
induced damage. In addition, CS@LGG relieved DNA Interestingly, we found that immunoglobulin secretion
damage and promoted intestinal epithelial proliferation, and functional pathways seemed to determine the CS@
as evidenced by IHC staining of Ki67 and γH2A.X LGG therapeutic effect. Consistently, in Figure 6G, KEGG
(Figure 3E, J and K). In summary, CS@LGG repaired pathways analysis showed downregulation of the intestinal
the intestinal barrier and protected the epithelium from immune network for IgA production, which was further
IR-induced proliferative suppression and DNA damage. confirmed by the GSEA results (Figure 6H and I). In
conclusion, one of the B-cell immune functions, IgA
Furthermore, we collected sufficient research evidence secretion, may be downregulated after CS@LGG treatment,
to demonstrate the biological safety of CS@LGG thereby preventing hyperactive immune reactions,
in vivo. During the 30-day gavage, the mice showed no promoting epithelial repair, and maintaining the intestinal
significant changes in major organs and body weight gain microenvironment. 36,37
(Figure 4A and B). For further safety tests of blood indexes,
we found a potential risk of abnormal declines in WBC and However, evidence on how the IgA pathway is inhibited,
PLT counts in the CS or LGG gavage groups (Figure 4F). its interaction with CS@LGG, and the specific influence of
Fortunately, this risk was completely avoided in the the microbiota composition remains insufficient. Some
CS@LGG group, due to the outstanding ability of CS to studies have shown that Lactobacillus probiotics can
confine LGG and itself from entering the blood circulation produce metabolites, such as short-chain fatty acids, 38,39
and causing systemic side effects. In addition, serum which also have therapeutic effects on radiation-induced
biochemical factors related to liver function (AST and ALT, bowel injury. However, the inter-relationship between
Figure 4D) remained unchanged in the biomaterial gavage the microbiota, metabolites, and the IgA pathway needs
group compared with LGG administration. This might be to be further explored. In addition, there is still a lack of
due to the special metabolic pathway of the microflora, validation in large animal models, such as pigs, Beagles,
named enterohepatic circulation, which allows bacteria or monkeys. In this regard, in-depth analyses combining
to reach the liver and biliary system instead of the kidney. metagenomics and metabolomics are required in future
Taken together, we demonstrated that CS@LGG prevented studies.
systemic toxicity and ensure long-term biosafety. 5. Conclusion

Unexpectedly, we found that this biopolymer protected
intestinal epithelial cells without promoting tumor With comprehensive integration of the advantages of
proliferation. Indeed, there is evidence of the anticancer probiotics and CS, this study designed a biosafe and
effect of Lactobacillus. 34,35 In Figure 5A, MC38 mice colon effective new probiotic biomaterial, CS@LGG, which
subcutaneous and orthotopic tumor models were treated can dramatically decrease the local and systemic pro-
differently, either with intratumor injection or gavage. inflammatory factors as well as relieve of oxidant-induced
However, the results in Figure 5C-H were similar, showing DNA damage. It can also repair a highly permeabilized
that the CS@LGG treatment group showed remarkable intestinal barrier without promoting tumor proliferation.
tumor shrinking with or without IR. In addition, we More significantly, it can also downregulate the local
performed in vitro experiments as shown in Figure 5B, B-cell response and IgA secretion to avoid overactivation
I, and J. Using CCK-8 and colony forming assays, we of local mucosal immunity and disruption of intestinal
found that MC38 tumor cells showed poor viability and microecology balance. To sum up, upon combination with
proliferation ability after CS@LGG treatment with or existing therapies, further optimization and innovation
without IR. On the contrary, IEC6 normal intestinal of CS@LGG endows itself with important clinical
cells remained in a well-growing state with abundant translational value for the treatment and relief of acute
colony formation. Comprehensively, the above evidence radiation-induced bowel injury.

Volume 3 Issue 3 (2025) 78 doi: 10.36922/ARNM025230026