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Polypeptide-engineered DNA tetrahedrons for targeting treatment of colorectal cancer via apoptosis and autophagy
- Source :
- Journal of controlled release : official journal of the Controlled Release Society. 309
- Publication Year :
- 2019
-
Abstract
- Smart delivery of therapeutic peptides that target cellular signaling pathways holds high specificity and great promise for cancer therapy. Here, DNA tetrahedrons (TDs) are designed to carry two therapeutic peptides-FAS peptide and FK-16 peptide. DNA TDs are designed with varied numbers and spatial placement of FAS peptides and FK-16 peptides, and tested for their anti-cancer efficacy. Trimerization of FAS receptors using TDs that are assembled with three FAS peptides enhances FAS-induced cell apoptosis. FK-16 peptides are conjugated to TDs via a peptide sequence sensitive to MMP-2/9 in tumor microenvironment. Therefore, FK-16 peptides are expected to detach from TDs once arrived the tumor microenvironment. A cell penetrating peptide (TAT) is also conjugated to the FK-16 peptide to facilitate its intracellular delivery, which increases the FK-16 peptide-induced cell apoptosis and autophagy. TD-3(TFM)3(FAS) (TFM: TAT + FK-16 + MMP-2/9) exhibits the highest HT-29 inhibition in vitro and in vivo among all therapies. In addition to the high anti-cancer efficacy, TD-3(TFM)3(FAS) shows a high specificity to HT-29 cells in vitro and in vivo. Low cell inhibition rates and cellular uptake are observed in normal cells. In sum, the multifunctional TD-3(TFM)3(FAS) provides a new platform for the smart delivery of anti-cancer peptides to achieve enhanced efficacy and high specificity.
- Subjects :
- Cell signaling
Cell
Pharmaceutical Science
Peptide
Antineoplastic Agents
Apoptosis
02 engineering and technology
Cell-Penetrating Peptides
03 medical and health sciences
medicine
Autophagy
Tumor Microenvironment
Humans
Peptide sequence
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Tumor microenvironment
Drug Carriers
DNA
021001 nanoscience & nanotechnology
Fas receptor
Cell biology
medicine.anatomical_structure
chemistry
Cell-penetrating peptide
0210 nano-technology
Colorectal Neoplasms
Peptides
HT29 Cells
Subjects
Details
- ISSN :
- 18734995
- Volume :
- 309
- Database :
- OpenAIRE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Accession number :
- edsair.doi.dedup.....5eefe14af428870066588332f134251d