PUBLICATION
Sequential Intercellular Delivery Nanosystem for Enhancing ROS-Induced Antitumor Therapy
- Authors
- Wang, B., Zhang, H., An, J., Zhang, Y., Sun, L., Jin, Y., Shi, J., Li, M., Zhang, H., Zhang, Z.
- ID
- ZDB-PUB-191218-17
- Date
- 2019
- Source
- Nano Letters 19: 3505-3518 (Journal)
- Registered Authors
- Zhang, Hongling
- Keywords
- Photodynamic therapy, extracellular vesicles, linoleic acid hydroperoxide, membrane fusion liposome, nano FeO, reactive oxygen species
- MeSH Terms
-
- Animals
- Antibiotics, Antineoplastic/administration & dosage*
- Antibiotics, Antineoplastic/therapeutic use
- Cell Line, Tumor
- Doxorubicin/administration & dosage
- Doxorubicin/analogs & derivatives*
- Doxorubicin/therapeutic use
- Drug Delivery Systems
- Female
- Linoleic Acids/administration & dosage*
- Linoleic Acids/therapeutic use
- Lipid Peroxides/administration & dosage*
- Lipid Peroxides/therapeutic use
- Mice, Inbred BALB C
- Neoplasms/drug therapy*
- Neoplasms/metabolism
- Polyethylene Glycols/administration & dosage
- Polyethylene Glycols/therapeutic use
- Reactive Oxygen Species/metabolism*
- Zebrafish
- PubMed
- 31034238 Full text @ Nano Lett.
Citation
Wang, B., Zhang, H., An, J., Zhang, Y., Sun, L., Jin, Y., Shi, J., Li, M., Zhang, H., Zhang, Z. (2019) Sequential Intercellular Delivery Nanosystem for Enhancing ROS-Induced Antitumor Therapy. Nano Letters. 19:3505-3518.
Abstract
Despite recent advances in enhancing photodynamic therapy efficacy, high-efficiency reactive oxygen species (ROS)-based therapy approach, especially in malignancy tumor treatment, remains challenging. Relieving the hypoxia of tumor tissue has been considered to be an attractive strategy for enhancing ROS-based treatment effect. Nevertheless, it is frequently neglected that the hypoxic regions are usually located deep in the tumors and therefore are usually inaccessible. To address these limitations, herein we constructed a sequential intercellular delivery system (MFLs/LAOOH@DOX) that consists of a membrane fusion liposomes (MFLs) doped with linoleic acid hydroperoxide (LAOOH) in the lipid bilayer and antitumor doxorubicin (DOX) encapsulated inside. In this report, LAOOH, one of the primary products of lipid peroxidation in vivo, was selected as ROS-generated agent herein, which depends on Fe2+ rather than oxygen and other external stimuli to produce ROS. Upon the enhanced permeation and retention effect, MFLs/LAOOH@DOX first fused with tumor cell membranes in the perivascular region in synchrony with selective delivery of LAOOH into the plasma membrane and the on-demand intracellular release of DOX. By hitchhiking with extracellular vesicles, LAOOH, as a cell membrane natural ingredient, spread gradually to neighboring cells and throughout the entire tumor eventually. Combined with subsequent administration of nano Fe3O4, ROS was specifically generated on the tumor cell membrane by LAOOH throughout the tumor tissues. This study offers a new method to enhance ROS-based antitumor treatment efficiency.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping