A novel combined therapeutic strategy of Nano-EN-IR@Lip mediated photothermal therapy and stem cell inhibition for gastric cancer

• Published in: Biomedicine & pharmacotherapy 2024-05, Vol.174, p.116486-116486, Article 116486
• Main Authors: Yang, Liping, Du, Yan-e, Liao, Fangli, Huang, Tong, Liu, Yadong, Liu, Junzhao, Wang, Can, Zhan, Zhu, Cao, Yang, Wang, Zhigang, Chen, Weixian
• Format: Article
• Language: English
• Subjects: Animals; Cancer stem cell; Cell Line, Tumor; Combined Modality Therapy; EN4; Gastric cancer; Humans; Indoles - chemistry; Indoles - pharmacology; Liposomes; Mice; Mice, Inbred BALB C; Mice, Nude; Nanocomposites - chemistry; Nanoliposome; Nanoparticles - chemistry; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - pharmacology; Photothermal Therapy - methods; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; PTT; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Stomach Neoplasms - therapy
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2024.116486

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. [Display omitted] •A combined therapeutic strategy of PTT and GCSC inhibition.•Nano-EN-IR@Lip loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor).•IR780-mediated PTT; EN4 synergistically inhibited the self-renewal and stemness of GCSCs.•Nano-EN-IR@Lip is biocompatible and exhibit superior PA imaging properties.•A novel clinical nanomedicine for the integration of GC diagnosis, treatment and prevention.