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
yht完成签到,获得积分10
1秒前
科研通AI2S应助清澄采纳,获得10
1秒前
1秒前
乐乐应助喵喵采纳,获得10
3秒前
3秒前
FashionBoy应助韭菜盒子采纳,获得10
5秒前
5秒前
超级灰狼发布了新的文献求助10
7秒前
YJY发布了新的文献求助10
8秒前
8秒前
猫咪也疯狂应助fifteen采纳,获得10
8秒前
janarbek完成签到,获得积分10
9秒前
酶没美镁发布了新的文献求助10
10秒前
13秒前
ayj完成签到,获得积分10
13秒前
15秒前
17秒前
18秒前
hokuto应助歌于心采纳,获得10
19秒前
今后应助PhDshi采纳,获得10
19秒前
badada完成签到,获得积分10
20秒前
20秒前
温婉的夏烟完成签到 ,获得积分10
21秒前
21秒前
谨慎不二完成签到,获得积分10
22秒前
22秒前
liian7发布了新的文献求助200
23秒前
March完成签到,获得积分10
24秒前
26秒前
筱溪完成签到 ,获得积分10
26秒前
27秒前
kangsynat完成签到 ,获得积分10
28秒前
星辰发布了新的文献求助10
28秒前
科研通AI2S应助零花钱采纳,获得10
29秒前
研友_VZG7GZ应助研友_nPoXoL采纳,获得10
29秒前
kxy完成签到,获得积分10
31秒前
李健的小迷弟应助ma采纳,获得10
31秒前
完美世界应助lan采纳,获得10
31秒前
科研通AI2S应助lan采纳,获得10
31秒前
Barton应助lan采纳,获得10
31秒前
高分求助中
Evolution 10000
ISSN 2159-8274 EISSN 2159-8290 1000
Becoming: An Introduction to Jung's Concept of Individuation 600
Ore genesis in the Zambian Copperbelt with particular reference to the northern sector of the Chambishi basin 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
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 3160952
求助须知:如何正确求助?哪些是违规求助? 2812175
关于积分的说明 7894698
捐赠科研通 2471057
什么是DOI,文献DOI怎么找? 1315853
科研通“疑难数据库(出版商)”最低求助积分说明 631036
版权声明 602068