纳米氧载体促进ATP响应化疗与ROS增效用于癌症治疗
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- 英文论文题名：Oxygen Nanocarrier-boosted ATP-responsive Chemotherapy with Amplified ROS Lethality for Combined Cancer Therapy
- 论文作者：赵鹏飞 ; 郑明彬 ; 罗震宇 ; 陈泽 ; 马轶凡 ; 蔡林涛
- 英文论文作者：Pengfei Zhao ; Mingbin Zheng ; Zhenyu Luo ; Ze Chen ; Yifan Ma ; Lintao Cai ; Guangdong Key Laboratory of Nanomedicine ; Shenzhen Institutes of Advanced Technology ; Chinese Academy of Sciences ; Department of Chemistry ; Guangdong Medical University
- 年：2016
- 作者机构：中科院深圳先进技术研究院广东省纳米医药重点实验室;广东医科大学药学院;
- 论文关键词：纳米氧载体 ; 血红蛋白 ; 适配体
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第三十八分会：纳米生物效应与纳米药物化学
- 语种：中文
- 分类号：R730.5
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第三十八分会 ; 纳米生物效应与纳米药物化学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：187k
- 原文格式：D
- 会议级别：全国
摘要
肿瘤细胞内三磷酸腺苷(ATP)和活性氧基团(ROS)的生成与细胞内氧浓度密切相关。本文通过聚合物的内核包载血红蛋白,阳离子的磷脂外壳吸附内嵌有阿霉素的DNA适配体,制备了具有优良载氧能力和ATP响应的核-壳型纳米氧载体A/D-ONC。结果表明,被细胞摄取后,载氧的A/D-ONC能够向肿瘤细胞提供充足氧气,上调细胞内ATP和ROS浓度水平。增量的ATP显著提高了ATP响应的阿霉素释放用于增强化疗,将对细胞生长有利的ATP转变为化疗的触发剂;同时增量的ROS提高了自身的细胞杀伤力。最终,联合增强化疗与ROS杀伤力的A/D-ONC实现了显著增强的细胞毒性,疗效为游离药物分子的4倍以上。A/D-ONC通过简单地氧气干预,将对细胞有利和有害的因素,转变或放大为对细胞有害的因素,实现了对肿瘤细胞"殊途同归"的杀伤作用,为新型肿瘤治疗提供了新的窗口。
The generation of ATP and ROS is closely related to the amount of oxygen in cancer cells. Herein, a novel hybrid nanocomposite(A/D-ONC) was developed with polymeric core entrapping hemoglobin and cationic shell absorbing doxorubicin(DOX)-intercalated DNA duplex. After cell endocytosis, oxygenated A/D-ONC donated abundant O_2 to mitochondria, which dramatically up-regulated intracellular ATP amount to promote the release of DOX from ATP-responsive A/D-ONC and successfully converted growth-beneficial ATP to the activator of detrimental chemotherapy, and apparently increased reactive oxygen species(ROS) content to amplify the cytotoxicity. Combining with both effects, A/D-ONC realized over 4-fold increase of lethality for half-maximal cancer cell inhibition compared with that of only DOX. By turning the growth-beneficial ATP to chemotherapy activator and amplifying ROS lethality, we created a novel ‘all road lead to Rome' drug delivery system for robust cancer therapy by O_2 interference.
The generation of ATP and ROS is closely related to the amount of oxygen in cancer cells. Herein, a novel hybrid nanocomposite(A/D-ONC) was developed with polymeric core entrapping hemoglobin and cationic shell absorbing doxorubicin(DOX)-intercalated DNA duplex. After cell endocytosis, oxygenated A/D-ONC donated abundant O_2 to mitochondria, which dramatically up-regulated intracellular ATP amount to promote the release of DOX from ATP-responsive A/D-ONC and successfully converted growth-beneficial ATP to the activator of detrimental chemotherapy, and apparently increased reactive oxygen species(ROS) content to amplify the cytotoxicity. Combining with both effects, A/D-ONC realized over 4-fold increase of lethality for half-maximal cancer cell inhibition compared with that of only DOX. By turning the growth-beneficial ATP to chemotherapy activator and amplifying ROS lethality, we created a novel ‘all road lead to Rome' drug delivery system for robust cancer therapy by O_2 interference.
引文
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