Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

Objective:To evaluate the effect of repeated intranasal insulin on postoperative delirium (POD) in elderly patients undergoing general anesthesia.Methods:Seventy elderly patients, aged ≥65 yr, with body mass index ≤28 kg/m 2, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, undergoing elective radical gastrectomy for gastric cancer under general anesthesia, were divided into 2 groups ( n=35 each) according to the random number table method: control group (group C) and insulin group (group I). In group C, normal saline 0.5 ml was administered intranasally twice a day from 2 days before surgery until the day of surgery.In group I, insulin 20 U (0.5 ml) was administered intranasally twice a day from 2 days before surgery until the day of surgery.The regional tissue oxygen saturation (rSO 2) was measured after entering the operating room (T 0), at intubation (T 1), at 1, 2 and 3 h after the start of operation (T 2-4), at the end of surgery (T 5) and at extubation (T 6). The insulin allergic reactions, nasal irritation and hypoglycemic reactions were recorded after intranasal administration of insulin or normal saline within 2 days before operation.The blood glucose concentrations were measured at T 0, T 3 and T 5.The occurrence of POD within 3 days after operation was recorded. Results:Compared with group C, the incidence of POD was significantly decreased within 3 days after operation, and the rSO 2 was increased at T 1-6 in group I ( P<0.05). The rSO 2 was significantly higher at T 1-6 than at T 0 in two groups ( P<0.05). There were no significant changes in blood glucose concentrations at T 0, T 3 and T 5 between the two groups ( P>0.05). No insulin allergic reactions, nasal irritation and hypoglycemic reactions occurred in two groups ( P>0.05). Conclusion:Repeated intranasal administration of insulin can increase the rSO 2 during operation and decrease the occurrence of POD in elderly patients undergoing radical gastrectomy for gastric cancer.