急性髓系白血病 (AML) 是一种髓系恶性肿瘤，其特征是疲劳、出血、感染或贫血等症状，如果不治疗可能致命。在 AML 中，酪氨酸激酶 (TK) 突变可提高肿瘤细胞的存活率。据报道，TK 最常见的突变出现在 Fms 样酪氨酸激酶 3 (FLT3)、Janus 激酶 2 (JAK2) 和 KIT（酪氨酸蛋白激酶 KIT）中，这使得这些 TK 成为 AML 中 TK 抑制剂 (TKI) 治疗的潜在靶点。 TK 中 30% 发生突变，突变的 FLT3 与较差的总体生存率和增加的治疗耐药性相关。 FLT3抑制剂用于治疗FLT3突变的AML，与低甲基化药物的组合显示出有希望的结果。 Midostaurin（MDS）是FLT3突变AML的第一个靶向治疗药物，其与化疗联合显示出良好的效果。然而，化疗会引起一些副作用，化疗的替代方案可能是使用纳米颗粒来更好地输送药物、提高生物利用度、降低耐药性和诱导毒性。本文的研究展示了装载 MDS 的金纳米粒子，并使用转染表达荧光素的 FLT3-ITD 突变 AML 细胞系 MV-4-11 Luc2，在体外和体内模型上比较其与单独 MDS 的功效。我们的临床前研究表明，通过在治疗的前半部分控制肿瘤生长，负载MDS的纳米粒子在体内模型上比游离药物具有更好的肿瘤抑制效果，而在治疗的后半部分，肿瘤大小与治疗的相当。免治疗队列。版权所有 © 2024 Munteanu、Tigu、Feder、Tatar、Gulei、Tomuleasa 和 Boca。

Acute myeloid leukemia (AML) is a malignancy in the myeloid lineage that is characterized by symptoms like fatigue, bleeding, infections, or anemia, and it can be fatal if untreated. In AML, mutations in tyrosine kinases (TKs) lead to enhanced tumor cell survival. The most frequent mutations in TKs are reported in Fms-like tyrosine kinase 3 (FLT3), Janus kinase 2 (JAK2), and KIT (tyrosine-protein kinase KIT), making these TKs potential targets for TK inhibitor (TKI) therapies in AML. With 30% of the mutations in TKs, mutated FLT3 is associated with poor overall survival and an increased chance of resistance to therapy. FLT3 inhibitors are used in FLT3-mutant AML, and the combination with hypomethylating agents displayed promising results. Midostaurin (MDS) is the first targeted therapy in FLT3-mutant AML, and its combination with chemotherapy showed good results. However, chemotherapies induce several side effects, and an alternative to chemotherapy might be the use of nanoparticles for better drug delivery, improved bioavailability, reduced drug resistance and induced toxicity. The herein study presents MDS-loaded gold nanoparticles and compares its efficacy with MDS alone, on both in vitro and in vivo models, using the FLT3-ITD-mutated AML cell line MV-4-11 Luc2 transfected to express luciferin. Our preclinical study suggests that MDS-loaded nanoparticles have a better tumor inhibitory effect than free drugs on in vivo models by controlling tumor growth in the first half of the treatment, while in the second part of the therapy, the tumor size was comparable to the cohort that was treatment-free.Copyright © 2024 Munteanu, Tigu, Feder, Tatar, Gulei, Tomuleasa and Boca.