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Outline
To achieve the co-delivery of water insoluble anti-tumor herbal components and enhance their anti-tumor efficacy, the natural polyphenolic compounds curcumin（Cur）and quercetin（Que）were co-assembled into curcumin-quercetin nanoparticles by carrier-free drug self-assembly technology.
The organic solution containing Cur and Que was added to an aqueous system by a drug liquid-phase self-assembly method to finally prepare curcumin-quercetin nanoparticles（Cur-Que NPs）. The morphology, particle size, phase properties and the stability of Cur-Que NPs were investigated by scanning electron microscopy（SEM）, X-ray powder diffraction（XRPD）and differential scanning calorimetry（DSC）. The self-assembly mechanism of Cur-Que was studied by Fourier transform infrared spectroscopy（FTIR）. The cytotoxicity of Cur-Que NPs on 4T1 cells was investigated by MTT assay. A 4T1 tumor-bearing mice model was established to study the combined anti-tumor efficacy of Cur-Que NPs in vivo.
The prepared Cur-Que NPs were amorphous and spherical with the particle size at（44.33 ± 12.18）nm. The lyophilized-treated Cur-Que NPs also remained spherical and the particle size was（44.53 ± 10.08）nm in SEM, indicating that the Cur-Que NPs had good stability. From the SEM, XRPD and DSC results, the morphology, particle size as well as existing forms of the lyophilized Cur-Que NPs remained unchanged for 6 months of storage at room temperature away from light, indicating that the Cur-Que NPs had good physical stability. From FTIR result, hydrogen bonding interaction was the driving force for the self-assembly of Cur-Que. Compared to other treatment groups, the Cur-Que NPs group showed significantly enhanced cytotoxicity（P < 0.001）. Also, the Cur-Que NPs group had the most significant inhibitory effect on tumor growth compared with the Cur API group or the Que API group（P < 0.05）.
Carrier-free Cur-Que NPs for self-assembly could achieve co-delivery for drugs and significantly improve anti-tumor efficacy.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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