Zhou Wenhui, Ma Xiaodong, Xiao Jianpeng, He Xiaohui, Liu Chang, Xu Xiaoyu, Viitala Tapani, Feng Jing, Zhang Hongbo
Shanghai Fengxian District Central Hospital Shanghai 201499 China.
Pharmaceutical Sciences Laboratory Åbo Akademi University 20520 Turku Finland.
Small Sci. 2024 Jan 29;4(3):2300192. doi: 10.1002/smsc.202300192. eCollection 2024 Mar.
Ovarian cancer remains a significant health issue worldwide, often facing limitations in treatment due to side effects and drug resistance. Tumor cells typically undergo the "Warburg effect," preferring glycolysis, which leads to their rapid growth and survival. Metformin, a widely used diabetes medication, targets 5' adenosine monophosphate-activated protein kinase (AMPK), reducing glycolysis and thereby slowing tumor growth. Additionally, forkhead box protein K2 (FOXK2), a transcription factor often found in excess in many tumors, promotes glycolysis and tumor development. Delivering metformin and FOXK2 siRNA directly to the tumor site in the body is challenging due to the metformin's poor water solubility and the fragile nature of siRNA. To address this, zirconium and 5,10,15,20-tetra(4-pyridyl)porphyrin nanoparticles loaded with FOXK2 siRNA, enveloped in cell membrane, co-encapsulated with metformin in gelatin methacrylate microspheres (ZrTCP@siFOXK2@CM/Met@GelMA) hydrogel microspheres are developed for effective dual delivery. These microspheres facilitate targeted drug delivery, photothermal therapy with near-infrared light, and interference with glucose metabolism. These results show that infrared light combined with metformin and FOXK2 siRNA successfully activates the AMPK pathway, reducing ovarian cancer growth. This method offers a promising new direction in treatment, utilizing the complex metabolic characteristics of ovarian cancer to achieve better results.
卵巢癌在全球范围内仍然是一个重大的健康问题，由于副作用和耐药性，其治疗常常面临局限。肿瘤细胞通常会经历“瓦伯格效应”，偏好糖酵解，这导致它们快速生长和存活。二甲双胍是一种广泛使用的糖尿病药物，作用于5' 腺苷单磷酸激活的蛋白激酶（AMPK），减少糖酵解，从而减缓肿瘤生长。此外，叉头框蛋白K2（FOXK2）是一种在许多肿瘤中经常过量存在的转录因子，它促进糖酵解和肿瘤发展。由于二甲双胍水溶性差以及siRNA性质脆弱，将二甲双胍和FOXK2 siRNA直接递送至体内肿瘤部位具有挑战性。为了解决这个问题，开发了负载FOXK2 siRNA的锆和5,10,15,20-四(4-吡啶基)卟啉纳米颗粒，包裹在细胞膜中，并与二甲双胍共包封在甲基丙烯酸明胶微球（ZrTCP@siFOXK2@CM/Met@GelMA）水凝胶微球中，以实现有效的双重递送。这些微球有助于靶向药物递送、近红外光光热疗法以及干扰葡萄糖代谢。这些结果表明，红外光联合二甲双胍和FOXK2 siRNA成功激活了AMPK通路，减少了卵巢癌的生长。这种方法利用卵巢癌复杂的代谢特征实现了更好的治疗效果，为治疗提供了一个有前景的新方向。
