Page 80 - ARNM-3-3

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

the collected colons in different groups were compared 3.4. CS@LGG has good biosafety in vivo
for length. As shown in Figure 2C and D, the PBS-gavage To ensure the possibility of clinical transformation, the
group (sham) suffered serious contracture, while CS@LGG long-term biosafety of CS@LGG and its main components
administration altered the phenotype. Statistically, this was studied. After a month of daily gavage with different
biomaterial was preferable to CS or LGG alone in reversing formulations, the weight gain of the mice was recorded,
colon contracture caused by IR. Surprisingly, we also found and their blood and major organs were harvested for
that the alleviative effect of the biomaterial was not only further assessment. The results indicated that the long-
observed locally in the intestinal tract but also systemically. term administration of CS, LGG, and CS@LGG caused
The weight gain (Figure 2E) and survival (Figure 2F) no obvious pathological changes in major organs shown
both demonstrated definite improvements. In addition, in HE staining (Figure 4A) and had no influence on
ELISA quantification of representative pro-inflammatory weight gain (Figure 4B). Furthermore, a blood test was
cytokines in radiation injury, including IL-6, TNFα, and conducted on the 30 day. Surprisingly, we found almost
th
IL-1β, as shown in Figure 2G and H, demonstrated the no adverse effects on the indexes of white blood cell
anti-inflammatory property of CS@LGG in colon tissues (WBC) proportion (Figure 4C). In addition, another index
and serum. (CREA-S and UREA) reflecting kidney function showed no

3.3. CS@LGG promotes the expression of tight significant differences among the treatments (Figure 4D).
junction proteins and repairs DNA damage to Unfortunately, the other two serum biochemical factors,
restore the intestinal barrier after IR aspartate transferase (AST) and alanine transferase
(ALT, Figure 4E), were unexpectedly raised in the LGG
Pathologically, one of the most significant abnormalities of gavage group, which suggested a negative impact on liver
radiation-induced early injury is intestinal barrier damage, function after long-term administration. Regarding the
especially at 3 days after IR. As shown by HE staining of the blood routine examination, results, such as red blood
mouse gut in Figure 3A, the IR + PBS group experienced cells (RBC), mean corpuscular hemoglobin (MCH), mean
the most serious damage in intestinal structure compared corpuscular hemoglobin concentration (MCHC), mean
with the other three treatments. Statistically, the sham cell volume (MCV), hemoglobin (HGB), and hematocrit
group demonstrated shortened intestinal villi, shallowed (HCT) were at normal levels (Figure 4F). Nevertheless, a
crypts, and a decreased ratio of length of villi to depth of potential impact might occur when LGG or CS was given
crypts, while CS@LGG administration greatly restored the alone, as shown by the abnormal reduction of WBC and
lesions in villi and crypts (Figure 3B-D). Moreover, early blood platelet (PLT) counts. Interestingly, this adverse
radiation-induced damage can also be seen in reduced effect paled in comparison when the CS macromolecule
regenerating crypt cells expressing Ki67 and damaged was combined with LGG. Indeed, polymeric compounds,
DNA in cells characterized by γH2A.X. As shown in such as CS can confine bacteria to the local intestinal
Figure 3E, IHC experiments revealed that the biomaterial mucosa, preventing systemic adverse reactions if LGG
promoted the expression of tight junction proteins CLDN3 accidentally enters the blood circulation. In summary,
and OCCLDN in the intestinal tract, both of which the application of macropolymer in delivering bacteria
are closely related to the intestinal barrier integrity. In effectively prevented the long-term toxicity caused by the
addition, the comet assay in Figure 3F demonstrated that exclusive administration of CS or LGG.
CS@LGG effectively reduced DNA damage caused by IR.
Subsequently, we used permeability tracer FITC-labeled 3.5. CS@LGG protects normal intestinal epithelium
dextran to further evaluate intestinal permeability. from IR without promoting tumor cell proliferation
As shown in Figure 3G, the irradiated gut with sham Radiation-induced bowel injury is commonly observed
treatment exhibited the highest permeability, whereas in patients undergoing pelvic radiotherapy for
CS@LGG treatment showed the lowest. These findings gastrointestinal cancer. Thus, we considered this clinical
indicate that CS@LGG restored the intestinal barrier setting and established two tumor models in C57BL/6
and prevented hyperpermeability caused by radiation- mice to simulate colon tumor radiotherapy (Figure 5A).
induced damage. As shown in Figure 3H-K, we observed MC38 tumor cell was implanted on both sides of the lower
increased Ki67 expression and reduced γH2A.X staining back subcutaneous tissue of mice until measurable. Both
in intestinal stem cell and epithelium, along with IHC tumors were then irradiated but treated differently with
staining and quantification of OCCLDN and CLDN3- PBS or CS@LGG intratumor injection every other day for
positive cells. Together, these results demonstrate that the self-controlled experiment. After 16 days, the tumors
CS@LGG could protect the intestinal tract from DNA were harvested, as illustrated in Figure 5B, and tumor
damage led induced by IR. volumes and weights were recorded (Figure 5C and D).

Volume 3 Issue 3 (2025) 72 doi: 10.36922/ARNM025230026