■化学-光动力联合疗法在癌症治疗中显示出显著的潜力。雷公藤甲素(TPL),一种天然来源的抗癌剂,当与光敏剂Chlorine6(Ce6)结合使用时,已显示提供增强的抗肿瘤益处。然而,用于共同递送TPL和Ce6的刺激响应性纳米载体的开发可以进一步增强这种联合治疗的疗效.
■在这项研究中,我们合成了一种pH/ROS双响应mPEG-TK-PBAE共聚物,其包含pH敏感的PBAE部分和ROS敏感的硫代(TK)键。通过自组装过程,TPL和Ce6成功共负载到mPEG-TK-PBAE纳米颗粒中,以下简称TPL/Ce6NPs。我们评估了pH和ROS敏感的药物释放和粒径变化。此外,我们研究了HepG2细胞增殖的体外抑制和凋亡的诱导,以及TPL/Ce6NPs在H22异种移植裸鼠中的体内抗肿瘤功效。
■mPEG-TK-PBAE共聚物是通过一锅法迈克尔加成反应合成的,并通过自组装成功地共包封了TPL和Ce6。暴露于酸性pH值和高ROS水平时,TPL/Ce6NPs中的有效载荷迅速释放。值得注意的是,释放的Ce6在激光照射下产生的丰富的ROS进一步加速了纳米系统的降解,从而放大肿瘤微环境响应性药物释放并增强抗癌功效。因此,TPL/Ce6NPs显著增加PDT诱导的HepG2细胞氧化应激和TPL诱导的凋亡,导致体外协同抗癌作用。此外,施用TPL/Ce6NPs(含0.3mg/kgTPL和4mg/kgCe6)七次,伴随着650nm激光照射,有效抑制H22荷瘤小鼠的肿瘤生长,同时表现出较低的全身毒性。
■总的来说,我们开发了一种肿瘤微环境响应性纳米系统,用于TPL和Ce6的共同递送,证明了化学-光动力疗法(chemo-PDT)对肝细胞癌(HCC)治疗的协同作用.
UNASSIGNED: Chemo-photodynamic combination therapy has demonstrated significant potential in the treatment of cancer. Triptolide (TPL), a naturally derived anticancer agent, when combined with the photosensitizer Chlorin e6 (Ce6), has shown to provide enhanced anti-tumor benefits. However, the development of stimuli-responsive nanovehicles for the co-delivery of TPL and Ce6 could further enhance the efficacy of this combination therapy.
UNASSIGNED: In this study, we synthesized a pH/ROS dual-responsive mPEG-TK-PBAE copolymer, which contains a pH-sensitive PBAE moiety and a ROS-sensitive thioketal (TK) linkage. Through a self-assembly process, TPL and Ce6 were successfully co-loaded into mPEG-TK-PBAE nanoparticles, hereafter referred to as TPL/Ce6 NPs. We evaluated the pH- and ROS-sensitive drug release and particle size changes. Furthermore, we investigated both the in vitro suppression of cellular proliferation and induction of apoptosis in HepG2 cells, as well as the in vivo anti-tumor efficacy of TPL/Ce6 NPs in H22 xenograft nude mice.
UNASSIGNED: The mPEG-TK-PBAE copolymer was synthesized through a one-pot Michael-addition reaction and successfully co-encapsulated both TPL and Ce6 by self-assembly. Upon exposure to acid pH values and high ROS levels, the payloads in TPL/Ce6 NPs were rapidly released. Notably, the abundant ROS generated by the released Ce6 under laser irradiation further accelerated the degradation of the nanosystem, thereby amplifying the tumor microenvironment-responsive drug release and enhancing anticancer efficacy. Consequently, TPL/Ce6 NPs significantly increased PDT-induced oxidative stress and augmented TPL-induced apoptosis in HepG2 cells, leading to synergistic anticancer effects in vitro. Moreover, administering TPL/Ce6 NPs (containing 0.3 mg/kg of TPL and 4 mg/kg of Ce6) seven times, accompanied by 650 nm laser irradiation, efficiently inhibited tumor growth in H22 tumor-bearing mice, while exhibiting lower systemic toxicity.
UNASSIGNED: Overall, we have developed a tumor microenvironment-responsive nanosystem for the co-delivery of TPL and Ce6, demonstrating amplified synergistic effects of chemo-photodynamic therapy (chemo-PDT) for hepatocellular carcinoma (HCC) treatment.