Page 84 - ARNM-3-3

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

In short, CS@LGG injection effectively inhibited tumor immune network for IgA production constitutes a critical
growth and proliferation in the self-controlled mouse part of the mechanism underlying CS@LGG’s curative effect
model while boosting radiotherapy simultaneously. In a on acute radiation-induced bowel injury. Furthermore, the
stricter and more typical sense, immune function within gene set enrichment analysis (GSEA) results (Figure 6H)
the tumor microenvironment is also an important factor also revealed key differential pathways between PBS and
affecting tumor growth. In this regard, the colon orthotopic CS@LGG gavage. Inflammatory pathways, such as the
tumor model described in Figure 5A was also taken into nuclear factor kappa B signaling pathway and the C-type
consideration for further analysis. After two weeks of tumor lectin receptor signaling pathway were both downregulated
implantation, the orthotopic tumors became measurable after gavage. In addition, IgA production in the intestinal
and were then grouped for different treatments. Finally, immune network also showed low-level expression. The
the colon orthotopic tumors were collected after 20 days of core gene clustering heatmap from GSEA (Figure 6I)
gavage (Figure 5E), and mouse weight gain was observed showed the specific differential genes expression between
with tumor volume being calculated (Figure 5F and G). the two groups, indicating that pro-inflammatory immune
Comprehensively, we concluded that CS@LGG effectively factors were sharply decreased after CS@LGG gavage.
suppressed tumor proliferation while protecting intestinal
cells from IR. In addition, we performed parallel in vitro 4. Discussion
experiments (Figure 5H-J). Cell viability of IEC6 and Acute radiation-induced bowel injury is a common adverse
MC38 was determined with CCK-8 assays (Figure 5H). effect of pelvic radiotherapy, delivering a “double blow” to
The results showed that 1 UI CS@LGG treatment enabled cancer patients during oncotherapy. More critically, there
2,7
normal intestinal cell IEC6 to recover from 8 Gy IR is still a lack of standard clinical treatments to deal with
while reducing the viability of colon tumor cell MC38. this problem. Nevertheless, inflammation relief and flora
In addition, a colony forming assay (Figure 5I and J) was regulation are the key principles in addressing radiation-
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conducted in the meantime. In comparison, CS@LGG induced bowel injury. In this regard, a new type of probiotic
treatment increased colony formation in normal cells while biomaterial was assembled in this study based on previous
decreasing it in tumor cells, with or without radiation. studies and present research. 25-27 This material features
easy synthesis, good biosafety, and low-cost raw materials.
3.6. CS@LGG repairs the gut mucus niche by Furthermore, with the Food and Drug Administration
inhibiting local immunoglobulin A (IgA) production approval of CS and LGG, there is a greater chance of clinical
to downregulate the inflammatory pathway translation and application of CS@LGG in radiotherapy.
To delineate the concrete mechanism by which CS@LGG Unfortunately, in the preliminary experiments, we observed
alleviates acute radiation-induced damage, we performed that probiotics alone fail to survive in gastric acid and
whole transcriptome sequencing with intestinal tissues digestive enzymes in vivo, while they are also fragile to
from different groups. The Venn diagram in Figure 6A external changes of temperature and pH. More concerningly,
displays differential and common genes, illustrating there have also been reported to potentially cause bacteremia
that only 42 genes were identical, while the other three in vivo, which would be a serious systemic adverse effect.
comparative combinations showed great differences. We For this reason, it is strongly recommended to choose one
then further analyzed the differential genes among groups. of the biomacromolecule carriers to maintain their viability,
The principal components analysis map (Figure 6B) and facilitate intestinal colonization, and optimize the curative
31
volcano plot (Figure 6C) showed the differences in gene effect. 28-30 Among many materials, CS is a preferred choice.
expression between PBS and CS@LGG administration. It can be used as an energy-supplying substance in vitro
The up- or downregulated genes were ranked according to and plays an important role in maintaining the activity of
log (TPM+1) in the heatmap (Figure 6B), and the specific probiotics. Its natural hydrogel property of water absorption
10
961 downregulated genes and 403 upregulated genes were can play an important role in protecting the damaged
plotted, as shown in Figure 6C. To explore the specific bowel barrier. 32,33 Indeed, the final products feature a
regulatory pathways, the most enriched GO terms were hydrogel structure (macroscopically in Figure 1F), with a
identified, including biological processes (Figure 6D), coated microstructure observable with SEM (Figure 1B).
molecular function (Figure 6E), and cellular component Furthermore, with zeta potential measurement, FTIR, and
(Figure 6F). Surprisingly, we found that immune XPS assay results displayed in Figure 1C-E, its interior
regulation, especially the immunoglobulin secretion composition was analyzed, and the principle of electrostatic
and function, played a key role in CS@LGG therapeutic adsorption was verified during construction.
effect. Coincidentally, KEGG pathway analysis (Figure 6G) To determine actual efficacy in radiated-injury alleviation,
reached the same conclusion, indicating that the intestinal we employed a C57BL/6 mouse model for experimentative

Volume 3 Issue 3 (2025) 76 doi: 10.36922/ARNM025230026