Upconversion nanoparticle-based optogenetic nanosystem for photodynamic therapy and cascade gene therapy

光敏剂 光动力疗法 转染 纳米探针 光遗传学 光子上转换 线粒体 癌细胞 材料科学 生物物理学 细胞 化学 细胞生物学 纳米技术 生物 纳米颗粒 生物化学 光化学 基因 癌症 光电子学 发光 神经科学 有机化学 遗传学
作者
Xinyue Song,Fengyan Li,Feng Tian,Linlin Ren,Qi Wang,Chengfang Jiang,Tao Yan,Shusheng Zhang
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:157: 538-550 被引量:16
标识
DOI:10.1016/j.actbio.2022.12.002
摘要

Most photosensitizer molecules used for the photodynamic therapy (PDT) are chemically-synthesized organic photosensitizer dyes which show several limitations such as unsatisfactory cell uptake, weak selectivity and off-target phototoxicity. Recently, genetically-encoded photosensitizers have attracted increasing attentions which provide the targeted cell elimination with single-cell precision. However, their applications are mainly limited by the shallow tissue penetration depth of the excitation light and the low cell apoptosis ratio. Herein, we developed a feasible upconversion nanoparticle (UCNP)-based optogenetic nanosystem with three-in-one functional integration: bio-imaging, NIR-triggered PDT and cascade gene therapy. Firstly, the mitochondria-targeted genetically-encoded photosensitizer was constructed and transfected into cancer cells. Then, the functional upconversion nanoprobe was constructed with the mitochondria targetability and then the siRNA was loaded on the surface of UCNPs via the reactive oxygen species (ROSs) sensitive chemical bond. After the transfection and incubation, both of the upconversion nanoprobe and the genetically-encoded photosensitizer were accumulated in the mitochondria of cancer cells. Under the NIR irradiation, the emission of UCNPs could excite the expressed protein photosensitizer to generate ROSs which then stimulated the release of siRNAs in a controllable manner, achieving PDT and cascade gene therapy. Since the generation of ROSs and the release of siRNA occurred in the mitochondria in-situ, the mitochondria-mediated cell apoptosis signal pathway would be activated to induce cell apoptosis and subsequently inhibit tumor growth. To the best of our knowledge, this is the first report about NIR laser-activated, organelle-localized genetically-encoded photosensitizers developed for cascade therapy, which will widen the application of optogenetic tools in the tumor therapy. The application of genetically-encoded photosensitizers in photodynamic therapy (PDT) is mainly limited by the shallow tissue penetration depth of the excitation light and unsatisfactory therapeutic performance. In this experiment, we developed an upconversion nanoparticles-based optogenetic nanosystem to enhance the PDT and cascade gene therapy for malignant tumors. The expressed genetically-encoded photosensitizers were accumulated in the mitochondria, which were activated in situ by the upconversion nanoprobe. Besides, the photogenerated reactive oxygen species (ROSs) stimulated the release of siRNAs in a controllable manner. To the best of our knowledge, this is the first report about NIR laser-activated, genetically-encoded photosensitizers developed for organelle-localized controllable cascade therapy. We hope this work can accelerate the application of genetically-encoded photosensitizers in the tumor therapy.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
马桶盖盖子完成签到 ,获得积分10
刚刚
unowhoiam完成签到 ,获得积分10
刚刚
fyjlfy完成签到 ,获得积分10
2秒前
鲁滨逊完成签到 ,获得积分10
2秒前
公西翠萱完成签到,获得积分10
6秒前
小知了完成签到,获得积分10
8秒前
Zhaowx完成签到,获得积分10
9秒前
科研通AI2S应助研友_LMBAXn采纳,获得10
9秒前
10秒前
11秒前
科研通AI2S应助何晓俊采纳,获得10
12秒前
宇宙飞船2436完成签到,获得积分10
12秒前
斯文寄松完成签到 ,获得积分10
14秒前
..完成签到 ,获得积分10
15秒前
lichen发布了新的文献求助10
16秒前
Jun完成签到 ,获得积分10
19秒前
NXZNXZ完成签到 ,获得积分10
21秒前
fanconi完成签到 ,获得积分10
23秒前
大个应助Kevin采纳,获得10
24秒前
曾珍完成签到 ,获得积分10
24秒前
lichen完成签到,获得积分10
25秒前
26秒前
爱听歌寄云完成签到 ,获得积分10
26秒前
Kaives完成签到 ,获得积分10
28秒前
英俊的铭应助Bonnie采纳,获得10
31秒前
哆啦A梦完成签到,获得积分10
31秒前
风雨无阻发布了新的文献求助10
32秒前
33秒前
脑洞疼应助戈壁滩的鱼采纳,获得10
34秒前
谨慎纸飞机完成签到,获得积分10
35秒前
drift完成签到,获得积分10
35秒前
风趣的惜天完成签到 ,获得积分10
36秒前
性温雅完成签到 ,获得积分10
36秒前
顾矜应助勤恳依霜采纳,获得10
37秒前
Kevin发布了新的文献求助10
39秒前
40秒前
40秒前
风雨无阻完成签到,获得积分10
41秒前
Bonnie完成签到,获得积分20
43秒前
44秒前
高分求助中
Sustainability in Tides Chemistry 2000
Microlepidoptera Palaearctica, Volumes 1 and 3 - 13 (12-Volume Set) [German] 1122
Дружба 友好报 (1957-1958) 1000
The Data Economy: Tools and Applications 1000
Mantiden - Faszinierende Lauerjäger – Buch gebraucht kaufen 700
PraxisRatgeber Mantiden., faszinierende Lauerjäger. – Buch gebraucht kaufe 700
A Dissection Guide & Atlas to the Rabbit 600
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3099819
求助须知:如何正确求助?哪些是违规求助? 2751306
关于积分的说明 7612410
捐赠科研通 2403104
什么是DOI,文献DOI怎么找? 1275188
科研通“疑难数据库(出版商)”最低求助积分说明 616276
版权声明 599053