Anti-melanoma effect and action mechanism of a novel chitosan-based composite hydrogel containing hydroxyapatite nanoparticles.

Hydroxyapatite nanoparticles (HANPs) have been increasingly regarded and reported due to their potential anti-tumor ability. Previously, we found that the rod-like HANPs had good application potential for cutaneous melanoma (CMM). To satisfy the actual requirements in repairing post-operative skin defects and inhibiting CMM recurrence after tumorectomy, we constructed a novel chitosan/alginate (CS/Alg) hydrogel containing the aforementioned HANPs. The in vitro cell experiments confirmed that activated mitochondrial-dependent apoptosis was tightly related to the anti-tumor ability of HANPs. Specifically, we further discovered several target proteins might be involved in abnormal activating Wnt, proteoglycans in cancer, oxidative phosphorylation and p53 signaling pathways. The in vivo animal experiments demonstrated that the HANPs-loaded CS/Alg hydrogel (CS/Alg/HANPs) had a similar effect on inhibiting tumor growth as HANPs, and CS/Alg hydrogel as well as phosphate buffered saline (PBS) group (control) not showed any effect, proving the key role of HANPs. The immunohistochemical staining demonstrated a tumor inhibition via the mitochondria-mediated apoptosis pathway, consistent with the in vitro evaluation. Moreover, CS/Alg/HANPs exhibited no additional biosafety risk to the functions of major organs. Overall, this CS/Alg/HANPs hydrogel has substantial application potential for treating CMM.