Preparation of a mitochondria-targeted and NO-releasing nanoplatform and its enhanced pro-apoptotic effect on cancer cells.
The therapeutic applications of exogenous nitric oxide are usually limited by its short half-life and its vulnerability to many biological substances, thus straightforward and precise spatiotemporal control of NO delivery may be critical to its therapeutic effects. Herein, the mitochondria-targeted and photoresponsive NO-releasing nanosystem is demonstrated as a new approach for cancer treatment. The nanosystem is fabricated by covalently incorporating a NO photo-donor and a mitochondria targeting ligand onto carbon-dots; accordingly, multi-functionalities (mitochondria-targeting, light-enhanced efficient NO-releasing, and cell imaging) are achieved. The in vitro NO release profiles for the nanosystem show that the duration of NO release from the present C-dot-based nanosystem containing immobilized SNO can be extended up to 8 hours or more. Upon cellular internalization, the nanosystem can target mitochondria and release NO. The action of the nanosystem on three cancer cell lines is evaluated; it is found that the targeted NO-releasing system can cause high cytotoxicity towards the cancer cells by specifically damaging their mitochondria. Additionally, light irradiation can amplify the cell apoptosis by enhancing NO release. These observations demonstrate that incorporating mitochondria-targeting ligand onto a NO-releasing system can enhance its pro-apoptosis action, thereby providing new insights for exploiting NO in cancer therapy.
College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, 510640, China.
Jiangsheng
J
Xu
Fang
F
Zeng
Hao
H
Wu
Caiping
C
Hu
Changmin
C
Yu
Shuizhu
S
Wu
D017209:Apoptosis; D002244:Carbon / Q000737:chemistry; D002470:Cell Survival; D004396:Coloring Agents / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008564:Membrane Potentials / Q000187:drug effects; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D009569:Nitric Oxide / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D010316:Particle Size; D010777:Photochemistry
D004396:Coloring Agents; D008024:Ligands; D009569:Nitric Oxide; D002244:Carbon; D010100:Oxygen
NO; apoptosis; cancer therapy; imaging; mitochondria