Tumor Microenvironment-Mediated Construction and Deconstruction of Extracellular Drug-Delivery Depots.
Nano Lett
; 16(2): 1118-26, 2016 Feb 10.
Article
in En
| MEDLINE
| ID: mdl-26785163
ABSTRACT
Protein therapy has been considered the most direct and safe approach to treat cancer. Targeting delivery of extracellularly active protein without internalization barriers, such as membrane permeation and endosome escape, is efficient and holds vast promise for anticancer treatment. Herein, we describe a "transformable" core-shell based nanocarrier (designated CS-NG), which can enzymatically assemble into microsized extracellular depots at the tumor site with assistance of hyaluronidase (HAase), an overexpressed enzyme at the tumor microenvironment. Equipped with an acid-degradable modality, the resulting CS-NG can substantially release combinational anticancer drugs-tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and antiangiogenic cilengitide toward the membrane of cancer cells and endothelial cells at the acidic tumor microenvironment, respectively. Enhanced cytotoxicity on MDA-MB-231 cells and improved antitumor efficacy were observed using CS-NG, which was attributed to the inhibition of cellular internalization and prolonged retention time in vivo.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Snake Venoms
/
Breast Neoplasms
/
Drug Delivery Systems
/
Gene Transfer Techniques
/
TNF-Related Apoptosis-Inducing Ligand
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nano Lett
Year:
2016
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA