Vitamin k3-Loaded Magnetic Nanoparticle-Mediated Synergistic Magnetothermodynamic Therapy Evokes Massive ROS and Immune Modulation for Augmented Antitumor Potential,ACS Applied Materials & Interfaces

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Vitamin k3-Loaded Magnetic Nanoparticle-Mediated Synergistic Magnetothermodynamic Therapy Evokes Massive ROS and Immune Modulation for Augmented Antitumor Potential
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-06-02 , DOI: 10.1021/acsami.3c01702
Anjali Chauhan ₁ , Km Anjaly ₂ , Anamika Saini _{1,

3} , Ravi Kumar _{4,

5} , Bijoy K Kuanr ₄ , Deepika Sharma ₁

Affiliation

Magnetic nanoparticle (MNP)-mediated magnetic hyperthermia (MHT) under an alternating magnetic field (AMF) causes tumor regression via reactive oxygen species (ROS) generation. However, less therapeutic efficacy has been reported due to the generation of low levels of ROS in a hypoxic tumor microenvironment. Therefore, improved treatments are required to generate relatively high levels of ROS to promote irreversible oxidative damage to the tumor cells. Herein, we report a magnetothermodynamic (MTD) therapy, as a robust and versatile approach for cancer treatment, by combining the magnetothermodynamic-related ROS and heat-related immunological effect in order to overcome the aforementioned obstacle. The synergistic therapy was achieved by the development of vitamin k3 (Vk3)-loaded copper zinc ferrite nanoparticles (Vk3@Si@CuZnIONPs) as an efficient MTD agent. The in vitro results unveiled that enhanced ROS production under the influence of AMF is a predominant aspect in yielding an assertive anticancer response. The in vivo antitumor response was assessed in an ectopic tumor model of A549 lung adenocarcinoma by MTD. The tumor inhibition rate of 69% was achieved within 20 days of MTD treatment, exhibiting complete tumor eradication within 30 days. The validation of antitumor response was marked by severe apoptosis (TUNEL, Caspase-3) in the Vk3@Si@CuZnIONPs + AMF-treated group. The higher expression level of heat shock proteins and proinflammatory cytokines (IL-6, TNF-α, IL-1α, IL-1β) was speculated to play a role in the activation of immune response for faster tumor regression in the MTD-treated group. Therefore, by implementing a dual ROS and heat-mediated immunogenic effect, the antitumor efficiency of future cancer magnetotherapies will be greatly enhanced.

中文翻译：

载有维生素 k3 的磁性纳米粒子介导的协同磁热力学疗法可激发大量 ROS 和免疫调节以增强抗肿瘤潜力

交变磁场 (AMF) 下磁性纳米粒子 (MNP) 介导的磁热疗 (MHT) 导致肿瘤消退活性氧 (ROS) 的产生。然而，由于在缺氧肿瘤微环境中产生低水平的 ROS，据报道治疗效果较低。因此，需要改进治疗以产生相对高水平的 ROS，以促进对肿瘤细胞的不可逆氧化损伤。在此，我们报告了磁热力学 (MTD) 疗法，作为一种强大且通用的癌症治疗方法，通过结合磁热力学相关的 ROS 和热相关的免疫效应来克服上述障碍。通过开发载有维生素 k3 (Vk3) 的铜锌铁氧体纳米粒子 (Vk3@Si@CuZnIONPs) 作为有效的 MTD 剂，实现了协同治疗。体外_结果表明，在 AMF 的影响下增强 ROS 的产生是产生积极抗癌反应的主要方面。在体内通过 MTD 在 A549 肺腺癌的异位肿瘤模型中评估抗肿瘤反应。MTD治疗20天内肿瘤抑制率达到69%，30天内肿瘤完全根除。在 Vk3@Si@CuZnIONPs + AMF 处理组中，抗肿瘤反应的验证以严重的细胞凋亡（TUNEL，Caspase-3）为标志。热休克蛋白和促炎细胞因子（IL-6、TNF-α、IL-1α、IL-1β）的更高表达水平被推测在 MTD 治疗组的免疫反应激活中发挥作用，以加快肿瘤消退. 因此，通过实现双重 ROS 和热介导的免疫原性效应，未来癌症磁疗的抗肿瘤效率将大大提高。

更新日期：2023-06-02

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