Nano-hydroxyapatite-evoked immune response synchronized with controllable immune adjuvant release for strengthening melanoma-specific growth inhibition.

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.

[Physiological Characteristics and Nitrogen and Phosphorus Uptake of Myriophyllum aquaticum Under High Ammonium Conditions].

Ammonium nitrogen (NH4+-N) at high concentrations is toxic to plants. In order to explore the NH4+-N tolerance of Myriophyllum aquaticum (M. aquaticum) and its ability of nitrogen (N) and phosphorus (P) uptake, this study used a nutrient solution with three NH4+-N levels (70, 210, 420 mg·L-1) to incubate M. aquaticum for 21 d. The characteristics of plant physiology and N and P uptake of M. aquaticum were measured. At NH4+-N of 70 mg·L-1, M. aquaticum grew healthily, and shoot height and biomass linearly increased with the increase incubation time. Relative shoot height and biomass of M. aquaticum were 40.56 cm and 17.82 g·hole-1 on day 21, respectively. Compared to the control with 70 mg·L-1 ammonium, malondialdehyde (MDA) content of M. aquaticum was significantly increased; chlorophyll and soluble sugar contents were also high at NH4+-N of 210 mg·L-1. M. aquaticum suffered from the NH4+-N stress. However, the stress of 210 mg·L-1 NH4+-N did not affect its normal growth and there was no significant difference in the relative growth rate of the shoot height and biomass compared with the control. At NH4+-N of 420 mg·L-1, MDA contents of M. aquaticum doubled and the shoot height and biomass growth rate were only 27.4% and 17.9% of those for 70 mg·L-1 NH4+-N, indicating that M. aquaticum was subjected to serious stress that caused unhealthy growth or even death. At three NH4+-N levels, the ranges of N and P content of M. aquaticum were 30.7-53.4 mg·g-1 and 3.8-7.7 mg·g-1, respectively, which indicated that M. aquaticum had a high uptake capacity of N and P. M. aquaticum is an ideal wetland plant that has a good application prospect for constructed wetlands in biological treatment of high-ammonia wastewater.