免疫系统
佐剂
黑色素瘤
粒细胞巨噬细胞集落刺激因子
体内
药理学
材料科学
生物相容性
免疫疗法
癌症研究
医学
免疫学
细胞因子
生物
生物技术
冶金
作者
Zhu Chen,Jing Deng,Jun Cao,Hongfeng Wu,Gang Feng,Ruolan Zhang,Ran Bin,Kun Hu,Huấn Cao,Xiangdong Zhu,Qian Zhang
标识
DOI:10.1016/j.actbio.2022.04.002
摘要
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.
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