Specific cell targeting with APRPG conjugated PEG–PLGA nanoparticles for treating ovarian cancer
Abstract
Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG-PLA and mPEG-PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative ζ-potential (-14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic.
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APRPG-modified PEG-PLA nanoparticles target over-expressed αvβ3 integrin during tumor angiogenesis and inhibit tumor angiogenesis.
“Wang et al. prepared APRPG polypeptide modified poly(ethylene glycol) polylactic acid (PEG-PLA) nanoparticles to encapsulate angiogenesis inhibitors, using APRPG peptides to specifically target the over-expressed αvβ3 integrin during tumor angiogenesis, and more conducive to the effective load to inhibit tumor angiogenesis.229”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [229]
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- Authors
- Wang, Y., Liu, P., Duan, Y., Yin, X., Wang, Q., Liu, X., Wang, X., Zhou, J., Wang, W., Qiu, L., & Di, W.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Yuhuangding Hospital (CN)
- Corresponding author
- Qiu, Lihua
- Di, Wen
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 35
- Issue
- 3
- Pages
- 983-992
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2091888247
- Cited by
- 56
- References
- 41
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 10 · 2014: 5
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- School of Medicine, Shanghai Jiao Tong University (12XJ10079)
- National Natural Science Foundation of China (81272568, 81101738, 81072138)
- Shanghai Municipal Health Bureau (20114168)
- Shanghai Municipal Education Commission (14YZ029)
- Science and Technology Commission of Shanghai Municipality (11nm0503000, 1052nm04800, 11DZ2211002, 13430722200)
- 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 › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- PLGA-PEG nanoparticles, ovarian cancer, TNP-470, angiogenesis inhibitors, tumor targeting, mPEG-PLA, endothelial tube formation, apoptosis, tumor growth inhibition, nanoparticle drug delivery
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, O-(Chloroacetylcarbamoyl)fumagillol, Animals, Cyclohexanes, Female, Humans, Neovascularization, Pathologic, Oligopeptides, Ovarian Neoplasms, Ovary, Polyethylene Glycols, Polyglycolic Acid, Sesquiterpenes, Drug Delivery Systems, Lactic Acid, Angiogenesis Inhibitors, Mice, Nanoparticles, Human Umbilical Vein Endothelial Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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