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Abstract The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe2+ (DOX-Fe2+), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe2+/sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs.

Abstract Voriconazole is a first‐line medicine for treating invasive fungal infections. We evaluated the pharmacokinetics (PK) and safety of single/multiple doses of voriconazole injection of Hailing Pharmaceutical Group (Test, T), an imitation of Vfend® (Reference, R). Healthy subjects (n = 36) randomly received a once‐daily dose of T or R 3 or 4 mg/kg on Day 1 (single dose), a once‐daily dose of T or R 6 mg/kg on Day 4, and then six consecutive days for twice‐daily doses of T or R 3 or 4 mg/kg (multiple doses). The plasma was collected up to 72 h at time points after dosing on Day 1/10. Samples were measured by the liquid chromatography tandem mass spectrometry method. PK parameters were confirmed according to a non‐compartmental model. The relationship between the PK profiles of T and R revealed the different behavior in 3‐ and 4‐mg/kg groups. After single/multiple doses in the 3‐mg/kg group, the mean value for the area under the plasma concentration–time curve (AUC0−t, AUC0−∞) of R is about twice T. However, there was a high degree of similarity in the 4‐mg/kg group. The maximum plasma concentration (Cmax) of T and R showed no noticeable difference in the two groups. The median Tmax of T and R were within 2.0–2.13 h in the 3‐mg/kg group and 2.0–2.17 h in the 4‐mg/kg group. Severe adverse events did not occur. No clinically significant differences were found in safety and tolerance between T and R. This clinical study indicated that voriconazole injection might provide a safer alternative medicine.