关键词: 磁性纳米粒子, 结直肠癌, 阿霉素, 水凝胶载药体系, 细胞凋亡

Abstract:

Objective To investigate the efficacy of ferro?based magnetic starch?loaded gel beads， composed of MgFe₂O₄ and cassava starch， in the treatment of colorectal cancer. Methods Sixteen SPF?grade 6?week?old male Balb/c mice were randomly assigned to four groups （n = 4 per group）： control， CMCS SA@MgFe₂O₄， doxorubicin， and CMCS SA@MgFe₂O₄@Dox. Mice in each group received normal saline， CMCS SA@MgFe₂O₄， doxorubicin， or CMCS SA@MgFe₂O₄@Dox on days 4， 6， 8， 10， 12， and 14 post?implantation of colorectal tumor cells （HCT116）. Tumor volume changes were monitored following treatment. TUNEL staining was performed to assess tumor tissue apoptosis. Immunohistochemistry was used to evaluate the expression levels of Ki67 and Caspase?3 in tumor tissues. Western blot was employed to determine the protein expression levels of Caspase?3， Bcl?2， and Bax. Results Mice in the Control and CMCS SA@MgFe₂O₄ groups exhibited the largest tumour volumes， with intact major organ structures， tightly arranged cells， normal nuclear morphology， and no significant inflammatory cell aggregation. In contrast， mice in the Dox group displayed shrunken tumour tissues， disorganized cardiac muscle fibres， enlarged interstitial spaces in splenic tissues， and inflammatory cell infiltration in liver， lung， and kidney tissues. Mice in the CMCS SA@MgFe₂O₄@Dox group showed minimal tumour tissue， well?aligned cardiac muscle fibres， and reduced inflammatory responses in the remaining organs. Compared to the Control group， mice in both the Dox and CMCS SA@MgFe₂O₄@Dox groups demonstrated significantly decreased tumour volume and final weight （P < 0.05）， increased interstitial inflammatory cell aggregation， decreased collagen fibres， and enhanced apoptosis. Additionally， there was a significant decrease in Ki67 expression （P < 0.05） and an increase in Caspase?3 expression （P < 0.05）. The expression of Bcl?2 protein was also significantly reduced （P < 0.05）， while the expression of Caspase?3 and Bax proteins was significantly increased （P < 0.05）. Compared to the Dox group， mice in the CMCS SA@MgFe₂O₄@Dox group exhibited significantly smaller tumour volume and final weight （P < 0.01）， more pronounced tissue necrosis， further reduction in collagen fibres， and a greater increase in apoptosis. There was also a more significant decrease in Ki67 expression （P < 0.05） and a more substantial increase in Caspase?3 expression （P < 0.05）. Furthermore， the expression of Bcl?2 protein was further decreased， while the expression of Caspase?3 and Bax proteins was further increased （P < 0.05）. Conclusion The iron?based magnetic starch drug delivery system has no therapeutic effect on tumor cells， but the combination with adriamycin can significantly increase the therapeutic effect of adriamycin and reduce its side effects.

Key words: magnetic nanoparticles, colorectal cancer, doxorubicin, hydrogel drug delivery system, apoptosis