Efficient treatment of colon cancer with codelivery of TRAIL and imatinib by liposomes

Abstract

To solve the problem of resistance of tumor cells to TRAIL and the inevitable side effects of imatinib during treatment, we successfully prepared a kind of multifunctional liposome that encapsulated imatinib in its internal water phase and inserted TRAIL on its membrane in this study, which named ITLPs. The liposomes appeared uniform spherical and the particle size was approximately 150 nm. ITLPs showed high accumulation in TRAIL-resistance cells and HT-29 tumor-bearing mice model. In vitro cytotoxicity assay results showed that the killing activity of HT-29 cells treated with ITLPs increased by 50% and confirmed that this killing activity was mediated by the apoptosis pathway. Through mechanism studies, it was found that ITLPs arrested up to 32.3% of cells in phase M to exert anti-tumor effects. In vivo anti-tumor study showed that ITLPs achieved 61.8% tumor suppression and little toxicity in the HT-29 tumor-bearing mice model. Overall results demonstrated that codelivery of imatinib and TRAIL via liposomes may be a prospective method in the treatment of the TRAIL-resistance tumor.

Keywords:

• Liposomes
• nanodrug; cancer
• drug delivery system
• trail
• imatinib

Author contributions

Rongrong Fu: Conceptualization, Methodology, Formal analysis, Writing – original draft; Rui Chang: Writing – review & editing, Methodology, Investigation; Andong Peng, Changshun Feng, Weifan Zhu, Yi Chen, and Xue Tian: Investigation, Methodology; Rui Wang and Hui Yan: Supervision, Project administration, Funding acquisition; Jun Li and Dianlong Jia: Writing – review & editing, Writing – final draft, Supervision, Project administration, Funding acquisition. The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript.

Institutional review board statement

The animal study protocol was approved by the Special Committee on Scientific Research Ethics of Liaocheng University (Approval Code: 2022111010; Approval Date: 1 November 2022).

Disclosure statement

The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

This work was supported by a grant from the Shandong Provincial Natural Science Foundation [ZR2021LSW001, ZR2020KH019, ZR2021MC017, ZR2021MB097], Youth Innovative Science and Technology Program of Shandong Colleges and University [2019KJM012], Shandong Province Postgraduate Education Quality Improvement Plan [SDYKC18097].