Rongrong Fu, Rui Chang, Andong Peng, Changshun Feng, Weifan Zhu, Yi Chen, Xue Tian, Rui Wang, Hui Yan, Dianlong Jia, Jun Li
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引用次数: 0
摘要
摘要:肿瘤坏死因子相关凋亡诱导配体(TRAIL)可通过与死亡受体相互作用诱导细胞凋亡。然而,TRAIL的半衰期较短,且肿瘤细胞对TRAIL具有抗药性,这限制了其治疗效果。研究表明,伊马替尼对结肠癌细胞株有效,并能增强TRAIL诱导的细胞凋亡。然而,其副作用在治疗过程中不可避免。为了解决这些问题,本研究成功制备了一种多功能脂质体,将伊马替尼包裹在其内部水相中,并在其膜上插入TRAIL,命名为ITLPs。脂质体呈均匀球形,粒径约为150 nm。ITLPs在TRAIL耐药细胞和HT-29肿瘤小鼠模型中表现出较高的蓄积性。体外细胞毒性实验结果表明,用ITLPs处理的HT-29细胞的杀伤活性提高了50%,并证实这种杀伤活性是由细胞凋亡途径介导的。通过机理研究发现,高达 32.3% 的细胞被 ITLPs 停滞在 M 期,从而发挥抗肿瘤作用。体内抗肿瘤研究表明,ITLPs在HT-29肿瘤小鼠模型中的抑瘤率为61.8%,毒性很小。总体结果表明,通过脂质体联合递送伊马替尼和TRAIL可能是治疗TRAIL耐药肿瘤的一种前瞻性方法。
Efficient treatment of colon cancer with codelivery of TRAIL and imatinib by liposomes.
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.
期刊介绍:
Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology.
Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as:
-Preformulation and pharmaceutical formulation studies
-Pharmaceutical materials selection and characterization
-Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation
-QbD in the form a risk assessment and DoE driven approaches
-Design of dosage forms and drug delivery systems
-Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies
-Drug delivery systems research and quality improvement
-Pharmaceutical regulatory affairs
This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.