PUBLICATION
Cancer-targeted and intracellular delivery of Bcl-2-converting peptide with functional macroporous silica nanoparticles for biosafe treatment
- Authors
- Wu, Y., Ge, P., Xu, W., Li, M., Kang, Q., Zhang, X., Xie, J.
- ID
- ZDB-PUB-200112-1
- Date
- 2020
- Source
- Materials science & engineering. C, Materials for biological applications 108: 110386 (Journal)
- Registered Authors
- Li, Mingyu
- Keywords
- Bcl-2-converting peptide, Cancer treatment, Folate receptor, Macroporous silica nanoparticles, Targeted delivery
- MeSH Terms
-
- Animals
- Antineoplastic Agents/administration & dosage*
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/pharmacokinetics
- Apoptosis/drug effects
- Drug Carriers/administration & dosage
- Drug Carriers/chemistry
- Drug Delivery Systems/methods
- Drug Liberation
- Embryo, Nonmammalian/drug effects
- Endocytosis/drug effects
- Folate Receptors, GPI-Anchored/metabolism
- Folic Acid/chemistry
- HEK293 Cells
- HeLa Cells
- Humans
- Intracellular Space/drug effects
- Intracellular Space/metabolism
- Microscopy, Electron, Transmission
- Mitochondria/drug effects
- Nanoparticles/administration & dosage*
- Nanoparticles/adverse effects
- Nanoparticles/chemistry*
- Oligopeptides/administration & dosage*
- Oligopeptides/chemistry
- Oligopeptides/pharmacokinetics
- Porosity
- Proto-Oncogene Proteins c-bcl-2/metabolism*
- Silicon Dioxide/chemistry
- Zebrafish/embryology
- PubMed
- 31923940 Full text @ Mater Sci Eng C Mater Biol Appl
Citation
Wu, Y., Ge, P., Xu, W., Li, M., Kang, Q., Zhang, X., Xie, J. (2020) Cancer-targeted and intracellular delivery of Bcl-2-converting peptide with functional macroporous silica nanoparticles for biosafe treatment. Materials science & engineering. C, Materials for biological applications. 108:110386.
Abstract
Therapeutic peptide, NuBCP-9 (N9) as a Bcl-2 functional converter, has been demonstrated to have the remarkable anticancer efficiency in Bcl-2-abundant cancer. However, it faced technical challenges in clinical use, such as the low bioavailability, the easily-destroyed bio-stability, and the insusceptibility to cellular interior. With the potential of mesoporous silica nanoparticles (MSNs) as the promising delivery vehicle of therapeutic macromolecules, we developed a kind of MSNs with the surface coating of folic acid (FA) for cancer cell targeting and with the macropore loading of N9 peptide for cancer therapy. Our results showed that the functional MSNs had the relatively greater biosafety than the naked MSNs in zebrafish models, leading to less than 30% embryo of death at 200 μg/ml, which could further specifically target the folate receptor (FR)-overexpressed cervical cancer HeLa cells instead of FR-negative normal embryonic kidney HEK 293T cells in a FA-competitive manner. N9 peptide with the delivery of functional MSNs could be internalized by HeLa cells, and co-localized with mitochondria in a Bcl-2-dependent manner. Moreover, N9 peptide delivered by FA-modified MSNs displayed the excellent anticancer efficiency with great selectivity, inducing approximately 52% HeLa cells into apoptosis. In summary, our results illustrated the potential of functional MSNs with large pore size as an efficient nanocarrier for the intracellular delivery of peptide drugs with targeting proteins to realize cancer therapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping