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Self-Assembly of Therapeutic Peptide into Stimuli-Responsive Clustered Nanohybrids for Cancer-Targeted Therapy
- Source :
- Adv Funct Mater
- Publication Year :
- 2020
-
Abstract
- Clinical translation of therapeutic peptides, particularly those targeting intracellular protein-protein interactions (PPIs), has been hampered by their inefficacious cellular internalization in diseased tissue. Therapeutic peptides engineered into nanostructures with stable spatial architectures and smart disease targeting ability may provide a viable strategy to overcome the pharmaceutical obstacles of peptides. This study describes a strategy to assemble therapeutic peptides into a stable peptide-Au nanohybrid, followed by further self-assembling into higher-order nanoclusters with responsiveness to tumor microenvironment. As a proof of concept, an anticancer peptide termed β-catenin/Bcl9 inhibitors is copolymerized with gold ion and assembled into a cluster of nanohybrids (pCluster). Through a battery of in vitro and in vivo tests, it is demonstrated that pClusters potently inhibit tumor growth and metastasis in several animal models through the impairment of the Wnt/β-catenin pathway, while maintaining a highly favorable biosafety profile. In addition, it is also found that pClusters synergize with the PD1/PD-L1 checkpoint blockade immunotherapy. This new strategy of peptide delivery will likely have a broad impact on the development of peptide-derived therapeutic nanomedicine and reinvigorate efforts to discover peptide drugs that target intracellular PPIs in a great variety of human diseases, including cancer.
- Subjects :
- Materials science
medicine.medical_treatment
media_common.quotation_subject
Peptide
02 engineering and technology
010402 general chemistry
01 natural sciences
Article
Targeted therapy
Biomaterials
Electrochemistry
medicine
Internalization
media_common
chemistry.chemical_classification
Tumor microenvironment
Wnt signaling pathway
Immunotherapy
021001 nanoscience & nanotechnology
Condensed Matter Physics
0104 chemical sciences
Electronic, Optical and Magnetic Materials
chemistry
Cancer research
Nanomedicine
0210 nano-technology
Checkpoint Blockade Immunotherapy
Subjects
Details
- ISSN :
- 1616301X
- Volume :
- 29
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Advanced functional materials
- Accession number :
- edsair.doi.dedup.....6876c867d6a854e3d11379756244869d