Abstract | BACKGROUND: METHODS: PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC-MS/MS. The in vitro physicochemical properties and in vivo anti- glioma effects of PTX/Aβ-CN-PMs were also well studied. RESULTS: The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood- brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti- glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona. CONCLUSIONS: The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti- glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery.
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Authors | Zhe-Ao Zhang, Xin Xin, Chao Liu, Yan-Hong Liu, Hong-Xia Duan, Ling-Ling Qi, Ying-Ying Zhang, He-Ming Zhao, Li-Qing Chen, Ming-Ji Jin, Zhong-Gao Gao, Wei Huang |
Journal | Journal of nanobiotechnology
(J Nanobiotechnology)
Vol. 19
Issue 1
Pg. 453
(Dec 28 2021)
ISSN: 1477-3155 [Electronic] England |
PMID | 34963449
(Publication Type: Journal Article)
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Copyright | © 2021. The Author(s). |
Chemical References |
- Amyloid beta-Peptides
- Antineoplastic Agents
- Apolipoproteins E
- Micelles
- Peptide Fragments
- Polyesters
- Protein Corona
- amyloid beta-protein (25-35)
- Polyethylene Glycols
- poly(lactide)
- Paclitaxel
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Topics |
- Amyloid beta-Peptides
(administration & dosage, chemistry, pharmacokinetics)
- Animals
- Antineoplastic Agents
(administration & dosage, chemistry, pharmacokinetics)
- Apolipoproteins E
(administration & dosage, chemistry, pharmacokinetics)
- Blood-Brain Barrier
(metabolism)
- Brain
(drug effects, metabolism)
- Cell Line
- Cell Survival
(drug effects)
- Drug Delivery Systems
- Glioma
(drug therapy, metabolism)
- Humans
- Mice
- Micelles
- Nanoparticles
(administration & dosage, chemistry)
- Paclitaxel
(administration & dosage, chemistry, pharmacokinetics)
- Peptide Fragments
(administration & dosage, chemistry, pharmacokinetics)
- Polyesters
(administration & dosage, chemistry, pharmacokinetics)
- Polyethylene Glycols
(administration & dosage, chemistry, pharmacokinetics)
- Protein Corona
(chemistry)
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