Concerns about the potential systematic toxicity limit the extensive application of traditional therapeutic drugs for
melanoma therapy, nano-
hydroxyapatite (nHA) with good biocompatibility and anti-
tumor ability could be an alternative choice. In this study, nHA was employed as an anti-
tumor biomaterial due to its
tumor-specific toxicity. Meanwhile,
granulocyte-macrophage colony-stimulating factor (
GM-CSF) served as the immune adjuvant to activate the immune response. The delivery platform was fabricated by co-encapsulation of both nHA and
GM-CSF into a biocompatible thermosensitive PLGA-
PEG-PLGA hydrogel. The results showed that the bio-activities of nHA and
GM-CSF could be well-maintained within the
hydrogel. Interestingly, the addition of nHA could attenuate the burst release of
GM-CSF due to possible
protein absorption capacity of nHA, which is beneficial for
GM-CSF sustainable release at the
tumor site, achieving boosted and prolonged anti-
tumor immunity. The in vitro and in vivo data demonstrated that nHA/
GM-CSF hydrogel exhibited greater potency to inhibit
tumor growth via enhanced CD8+ T-cell response compared with
hydrogel and nHA
hydrogel groups, contributed by the synergistic effects of nHA and
GM-CSF. Overall, the strategy combining nHA and immune adjuvant shows great promise, which largely broadens the choice of combinational
therapies for
melanoma. STATEMENT OF SIGNIFICANCE: Nano-
hydroxyapatite (nHA) has been confirmed to specifically inhibit
melanoma tumor growth and induce immune response. However, its antitumor efficiency and immunity-evoking capacity are limited. In this study,
granulocyte-macrophage colony-stimulating factor (
GM-CSF) was introduced to serve as the immune adjuvant. Both of them were encapsulated into a biocompatible thermosensitive PLGA-
PEG-PLGA hydrogel. The addition of nHA could attenuate the burst release of
GM-CSF due to the interaction with nHA, which is beneficial for
GM-CSF sustainable release at
tumor site, achieving boosted and prolonged anti-
tumor immunity. Anti-
tumor immune response could be activated due to the release of
tumor-associated
antigen and
tumor debris induced by the specifically
tumor inhibition effect of nHA and
GM-CSF. The combination of nHA and
GM-CSF could play synergistic inhibiting effect on
tumor growth via boosting and prolonging anti-
tumor immunity.