Back to Search
Start Over
Self-accelerating H 2 O 2 -responsive Plasmonic Nanovesicles for Synergistic Chemo/starving therapy of Tumors.
- Source :
-
Theranostics [Theranostics] 2020 Jul 09; Vol. 10 (19), pp. 8691-8704. Date of Electronic Publication: 2020 Jul 09 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Rationale: Nanoscale vehicles responsive to abnormal variation in tumor environment are promising for use in targeted delivery of therapeutic drugs specifically to tumor sites. Herein, we report the design and fabrication of self-accelerating H <subscript>2</subscript> O <subscript>2</subscript> -responsive plasmonic gold nanovesicles (GVs) encapsulated with tirapazamine (TPZ) and glucose oxidase (GOx) for synergistic chemo/starving therapy of cancers. Methods: Gold nanoparticles were modified with H <subscript>2</subscript> O <subscript>2</subscript> -responsive amphiphilic block copolymer PEG <subscript>45</subscript> - b -PABE <subscript>330</subscript> by ligand exchange. The TPZ and GOx loaded GVs (TG-GVs) were prepared through the self-assembly of PEG <subscript>45</subscript> - b -PABE <subscript>330</subscript> -grafted nanoparticles together with TPZ and GOx by solvent displacement method. Results: In response to H <subscript>2</subscript> O <subscript>2</subscript> in tumor, the TG-GVs dissociate to release the payloads that are, otherwise, retained inside the vesicles for days without noticeable leakage. The released GOx enzymes catalyze the oxidation of glucose by oxygen in the tumor tissue to enhance the degree of hypoxia that subsequently triggers the reduction of hypoxia-activated pro-drug TPZ into highly toxic free radicals. The H <subscript>2</subscript> O <subscript>2</subscript> generated in the GOx-catalyzed reaction also accelerate the dissociation of vesicles and hence the release rate of the cargoes in tumors. The drug-loaded GVs exhibit superior tumor inhibition efficacy in 4T1 tumor-bearing mice owing to the synergistic effect of chemo/starvation therapy, in addition to their use as contrast agents for computed tomography imaging of tumors. Conclusion: This nanoplatform may find application in managing tumors deeply trapped in viscera or other important tissues that are not compatible with external stimulus (e.g. light).<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Animals
Breast Neoplasms diagnostic imaging
Breast Neoplasms metabolism
Cell Line, Tumor
Drug Synergism
Female
Glucose Oxidase chemistry
Glucose Oxidase pharmacology
Humans
Metal Nanoparticles
Mice
Tirapazamine chemistry
Tirapazamine pharmacology
Tomography, X-Ray Computed
Tumor Hypoxia drug effects
Xenograft Model Antitumor Assays
Breast Neoplasms drug therapy
Glucose Oxidase administration & dosage
Gold chemistry
Hydrogen Peroxide metabolism
Tirapazamine administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1838-7640
- Volume :
- 10
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Theranostics
- Publication Type :
- Academic Journal
- Accession number :
- 32754272
- Full Text :
- https://doi.org/10.7150/thno.45392