A multifunctional nanoplatform delivering carbon monoxide and a cysteine protease inhibitor to mitochondria under NIR light shows enhanced synergistic anticancer efficacy

Photoactivated chemotherapy has attracted widespread attention due to its ability to circumvent the shortcomings of hypoxia in tumor tissues compared with traditional photodynamic therapy. In this work, novel multifunctional nanoplatform (1), Ru-inhibitor@TPPMnCO@N-GQDs, was designed and prepared, w...

Full description

Saved in:
Bibliographic Details
Published in:Nanoscale 2022-06, Vol.14 (25), p.997-913
Main Authors: Tang, Qi, Liu, Jing, Wang, Cheng-Bin, An, Lu, Zhang, Hai-Lin, Wang, Yi, Ren, Bing, Yang, Shi-Ping, Liu, Jin-Gang
Format: Article
Language:English
Subjects:
Anticancer properties
Biocompatibility
Cancer
Carbon monoxide
Cysteine
Fluorescence
Graphene
Hypoxia
Infrared lasers
Light irradiation
Mitochondria
Near infrared radiation
Photodynamic therapy
Protease
Protease inhibitors
Quantum dots
Radiation damage
Ruthenium
Side effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Photoactivated chemotherapy has attracted widespread attention due to its ability to circumvent the shortcomings of hypoxia in tumor tissues compared with traditional photodynamic therapy. In this work, novel multifunctional nanoplatform (1), Ru-inhibitor@TPPMnCO@N-GQDs, was designed and prepared, which was capable of mitochondria-targeted co-delivery of the cysteine protease inhibitor and carbon monoxide (CO) stimulated with an 808 nm near infrared (NIR) laser. Nanoplatform (1) was prepared by covalent attachment of a mitochondria-targeted CO donor (TPPMnCO) and a Ru( ii )-caged cysteine protease inhibitor (Ru-inhibitor) on the surface of fluorescent N-doped graphene quantum dots (N-GQDs). Nanoplatform (1) preferentially accumulated in the mitochondria of cancer cells and instantly delivered CO and the cysteine protease inhibitor upon 808 nm NIR light irradiation, thus damaging mitochondria and leading to significant in vitro and in vivo anticancer efficacy. In addition, nanoplatform (1) has good biocompatibility and did not exert any toxic side effects on mice during the period of treatment. The targeted subcellular mitochondrial co-delivery of CO and the cysteine protease inhibitor may provide new insights into CO and enzyme inhibitor combined therapies for cancer treatment. A fluorescent nanoplatform covalently functionalized with a Mn-CO donor and a Ru( ii )-caged cysteine protease inhibitor delivers CO and the enzyme inhibitor to mitochondria upon NIR light irradiation, showing enhanced synergistic anticancer efficacy.
ISSN:2040-3364
2040-3372
DOI:10.1039/d2nr01122k