Lanthanum-Doped Chitosan Hydrogels Promote the Apoptosis of Melanoma Cells by Bcl-2/Bax Pathway

The surgical resection of melanoma may cause skin wounds, and the remaining melanoma cells bring a great risk of tumor recurrence. To overcome the above problem, we for the first time constructed lanthanum-doped chitosan (La-CS) hydrogels with excellent wound healing and antitumor functions. The La element was uniformly dispersed within whole hydrogels, and part of La3+ ions reacted with CS to form La-CS complex. The complexation interaction between La3+ ions and CS significantly improve the La3+ release performances of La-CS hydrogels. The as-released La3+ ions from the composite hydrogels selectively inhibited the proliferation of B-16 melanoma cells, but showed lower toxic side effects to L929 skin fibroblast cells. Moreover, the La3+ ions triggered the apoptosis of B-16 cells through Bcl-2/Bax pathway, as confirmed by the Annexin Vand PI double staining, flow cytometry, and Western blot results. The in vivo tumor models of C57 mice revealed that the La-CS hydrogels had more significant relapse-inhibition effects on B-16 melanoma cells than the pure CS hydrogels. At the same time, the in vivo wound healing was accelerated by the multifunctional hydrogels. The exciting finding provides a critical and promising strategy in the construction of La-doped hydrogels for oncotherapy.