Tumor Specific Delivery and Therapy by Double-Targeted Nanostructured Lipid Carriers with Anti-VEGFR-2 Antibody
Abstract
Vascular endothelial growth factor receptors (VEGFRs) are overexpressed on the surface of a variety of tumor cells and on tumor neovasculature in situ, which are potential targets for "double targeting" (tumor- and vascular-targeting) tumor therapy. This study aimed to develop a VEGFR-mediated drug delivery system to target chemotherapeutic agents to VEGFR-overexpressed tumor cells and tumor neovasculature endothelial cells in vitro and in vivo. An antibody modified docetaxel (DTX)-loaded targeted nanostructured lipid carrier (tNLC) was designed and prepared with DSPE-PEG-NH(2) as linker. The cellular cytotoxicity, cellular uptake, in vivo therapeutic effect and biodistribution of tNLC were investigated. The tNLC showed a particle size about 168 nm with encapsulation efficiency >95%, drug loading 5.55 ± 0.06% (w/w) and an average ligand coupling efficiency of 3.34 ± 2.63%. Cytotoxicity of tNLC against three human cell lines and one murine malignant melanoma was superior to that of Duopafei and nontargeted NLC (nNLC). The tNLC also showed better tolerance and antitumor efficacy in a murine model bearing B16 compared with Duopafei or nNLC. The studies on cellular uptake and biodistribution indicated that the better antitumor efficacy of tNLC was attributed to the increased accumulation of drug in both tumor and tumor vasculature. These findings suggested that tNLC designed to bind specifically to VEGFR-2 can be used to deliver DTX to the tumor vasculature and tumor and may inhibit tumor growth.
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Anti-VEGFR-2 antibody-modified lipid carrier can effectively deliver docetaxel (DTX) to the tumor vasculature and tumor, and inhibit tumor growth.
“They modified the lipid carrier with anti-VEGFR-2 antibody, which can effectively deliver docetaxel (DTX) to the tumor vasculature and tumor, and inhibit tumor growth.200”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [200]
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- Authors
- Liu, D., Liu, F., Liu, Z., Wang, L., & Zhang, N.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Zhang, Na
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-10-26
- Volume
- 8
- Issue
- 6
- Pages
- 2291-2301
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W1989392234
- Cited by
- 108
- References
- 37
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 2 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 8 · 2016: 10 · 2015: 9 · 2014: 12 · 2013: 8 · 2012: 8
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- nanostructured lipid carriers, VEGFR2, docetaxel, targeted drug delivery, tumor neovasculature, tumor targeting, vascular targeting, antibody-drug conjugates, melanoma, B16 melanoma, tissue distribution, cellular uptake, antitumor efficacy
- MeSH terms
- Docetaxel, Animals, Antibodies, Monoclonal, Antineoplastic Agents, Drug Carriers, Female, Flow Cytometry, Humans, Infusion Pumps, Lipids, Magnetic Resonance Spectroscopy, Drug Delivery Systems, Inhibitory Concentration 50, Vascular Endothelial Growth Factor Receptor-2, Taxoids, Cell Line, Tumor, Microscopy, Electron, Transmission, Cell Proliferation, Nanostructures, Mice
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