关键词: Cancer stem cell EN4 Gastric cancer Nanoliposome PTT

Mesh : Stomach Neoplasms / pathology therapy drug therapy Neoplastic Stem Cells / drug effects pathology Humans Photothermal Therapy / methods Animals Cell Line, Tumor Liposomes Photosensitizing Agents / pharmacology administration & dosage Indoles / pharmacology chemistry Nanoparticles / chemistry Mice, Nude Combined Modality Therapy Mice Mice, Inbred BALB C Proto-Oncogene Proteins c-myc / metabolism genetics Nanocomposites / chemistry

来  源:   DOI:10.1016/j.biopha.2024.116486

Abstract:
Recurrence and metastasis of gastric cancer is a major therapeutic challenge for treatment. The presence of cancer stem cells (CSCs) is a major obstacle to the success of current cancer therapy, often leading to treatment resistance and tumor recurrence and metastasis. Therefore, it is important to develop effective strategies to eradicate CSCs. In this study, we developed a combined therapeutic strategy of photothermal therapy (PTT) and gastric cancer stem cells (GCSCs) inhibition by successfully synthesizing nanoliposomes loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor). The nanocomposites are biocompatible and exhibit superior photoacoustic (PA) imaging properties. Under laser irradiation, IR780-mediated PTT effectively and rapidly killed tumor cells, while EN4 synergistically inhibited the self-renewal and stemness of GCSCs by suppressing the expression and activity of the pluripotent transcription factor c-Myc, preventing the tumor progression of gastric cancer. This Nano-EN-IR@Lip is expected to be a novel clinical nanomedicine for the integration of gastric cancer diagnosis, treatment and prevention.
摘要:
胃癌的复发和转移是治疗的主要挑战。癌症干细胞(CSC)的存在是当前癌症治疗成功的主要障碍。常导致治疗耐药和肿瘤复发转移。因此,重要的是制定有效的策略来根除CSC。在这项研究中,我们通过成功合成负载有IR780(光敏剂)和EN4(c-Myc抑制剂)的纳米脂质体,开发了光热疗法(PTT)和胃癌干细胞(GCSCs)抑制的联合治疗策略.纳米复合材料是生物相容的并且表现出优异的光声(PA)成像特性。在激光照射下,IR780介导的PTT有效和快速杀死肿瘤细胞,EN4通过抑制多能转录因子c-Myc的表达和活性,协同抑制GCSCs的自我更新和干性,预防胃癌的肿瘤进展。这种Nano-EN-IR@Lip有望成为整合胃癌诊断的新型临床纳米医学,治疗和预防。
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