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Cited by 127Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsGlioma Diagnosis and Treatment

The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.

Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting

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Chu, Liuxiang, Wang, Aiping, Ni, Ling, Yan, Xiuju, Song, Yina, Zhao, Mingyu, Sun, Kaoxiang, Mu, Hongjie, Liu, Sha, Wu, Zimei, Zhang, Chunyan·2018·Drug Delivery
DOI 10.1080/10717544.2018.1494226PMC PMC6127843
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Abstract

Glioblastoma is the most common malignant brain tumor. Efficient delivery of drugs targeting glioblastomas remains a challenge. Ephrin type-A receptor 3 (EPHA3) tyrosine kinase antibody-modified polylactide-co-glycolide (PLGA) nanoparticles (NPs) were developed to target glioblastoma via nose-to-brain delivery. Anti-EPHA3-modified, TBE-loaded NPs were prepared using an emulsion-solvent evaporation method, showed a sustained in vitro release profile up to 48 h and a mean particle size of 145.9 ± 8.7 nm. The cellular uptake of anti-EPHA3-modified NPs by C6 cells was significantly enhanced compared to that of nontargeting NPs (p < .01). In vivo imaging and distribution studies on the glioma-bearing rats showed that anti-EPHA3-modified NPs exhibited high fluorescence intensity in the brain and effectively accumulated to glioma tissues, indicating the targeting effect of anti-EPHA3. Glioma-bearing rats treated with anti-EPHA3-modified NPs resulted in significantly higher tumor cell apoptosis (p < .01) than that observed with other formulations and prolonged the median survival time of glioma-bearing rats to 26 days, which was 1.37-fold longer than that of PLGA NPs. The above results indicated that anti-EPHA3-modified NPs may potentially serve as a nose-to-brain drug carrier for the treatment of glioblastoma.

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Crossref · 10.1080/10717544.2018.1494226

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Figures

Figure 1. In vitro TBE release profiles of free TBE, P-TBE-NPs, T/P-TBE-NPs, and anti-EPHA3-T/P-TBE-NPs.
Figure 1. In vitro TBE release profiles of free TBE, P-TBE-NPs, T/P-TBE-NPs, and anti-EPHA3-T/P-TBE-NPs.CC BY · PubMed Central
Figure 2. (A) Fluorescence microscopy images of C6 cells incubated with Nile red-loaded NPs. (B) Mean percentages of coumarin-6 NP uptake by C6 cells, as determined by flow cytometry. Values represent the mean ± SD (n = 3). **p < .01 versus P-NPs; ##p < .01 versus T/P-NPs. NPs: nanoparticles.
Figure 2. (A) Fluorescence microscopy images of C6 cells incubated with Nile red-loaded NPs. (B) Mean percentages of coumarin-6 NP uptake by C6 cells, as determined by flow cytometry. Values represent the mean ± SD (n = 3). **p < .01 versus P-NPs; ##p < .01 versus T/P-NPs. NPs: nanoparticles.CC BY · PubMed Central
Figure 3. In vivo and brain distribution of DiR- and coumarin-6-loaded NPs in glioma-bearing rats. (A) In vivo fluorescence imaging at predetermined time points after intranasal administration of DiR-loaded NPs. (B) In vivo and excised tissues imaging of anti-EPHA3-modified DiR-loaded NPs at 4 h after intranasal and intravenous administration. (C) Fluorescence microscopy images of the brain, acquired 4 h after intranasal administration of coumarin-6-loaded NPs to glioma-bearing rats. Green: coumarin-6; blue: Hoechst 33342 (nuclei); yellow arrows point to the tumor site. DiR, 1,-1-dioctadecyl-3,-3,-3′,-3′-tetramethylindotricarbocyanine; NPs: nanoparticles.
Figure 3. In vivo and brain distribution of DiR- and coumarin-6-loaded NPs in glioma-bearing rats. (A) In vivo fluorescence imaging at predetermined time points after intranasal administration of DiR-loaded NPs. (B) In vivo and excised tissues imaging of anti-EPHA3-modified DiR-loaded NPs at 4 h after intranasal and intravenous administration. (C) Fluorescence microscopy images of the brain, acquired 4 h after intranasal administration of coumarin-6-loaded NPs to glioma-bearing rats. Green: coumarin-6; blue: Hoechst 33342 (nuclei); yellow arrows point to the tumor site. DiR, 1,-1-dioctadecyl-3,-3,-3′,-3′-tetramethylindotricarbocyanine; NPs: nanoparticles.CC BY · PubMed Central
Figure 4. Effects of treatments with TBE-loaded NPs on glioma-bearing rats. (A) Survival curves of glioma-bearing rats after different treatments (n = 10 each). (B) Apoptosis of glioma cells in glioma-bearing rats treated with saline, free TBE, P-TBE-NPs, T/P-TBE-NPs, and anti-EPHA3-T/P-TBE-NPs. Brown: apoptotic tumor cells; blue: tumor cells; red arrows point to apoptotic cells. (C) Quantification of apoptosis in rats treated with different formulations. Values represent the mean ± SD (n = 3). *p < .05 and **p < .01 versus P-TBE-NPs; #p < .05 versus T/P-TBE-NPs. NPs: nanoparticles; TBE: temozolomide butyl ester.
Figure 4. Effects of treatments with TBE-loaded NPs on glioma-bearing rats. (A) Survival curves of glioma-bearing rats after different treatments (n = 10 each). (B) Apoptosis of glioma cells in glioma-bearing rats treated with saline, free TBE, P-TBE-NPs, T/P-TBE-NPs, and anti-EPHA3-T/P-TBE-NPs. Brown: apoptotic tumor cells; blue: tumor cells; red arrows point to apoptotic cells. (C) Quantification of apoptosis in rats treated with different formulations. Values represent the mean ± SD (n = 3). *p < .05 and **p < .01 versus P-TBE-NPs; #p < .05 versus T/P-TBE-NPs. NPs: nanoparticles; TBE: temozolomide butyl ester.CC BY · PubMed Central

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  1. Baker S, 1999, Clin Cancer Res, 5, 309

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Metadata

Authors
Chu, L., Wang, A., Ni, L., Yan, X., Song, Y., Zhao, M., Sun, K., Mu, H., Liu, S., Wu, Z., & Zhang, C.
Affiliations
  • Yantai University (CN)
  • Luye Pharma (China) (CN)
Corresponding author
  • Wang, Aiping
  • Sun, Kaoxiang
ORCID
Venue
Drug Delivery
Publisher
Informa UK Limited
Published
2018-01-01
Volume
25
Issue
1
Pages
1634-1641
ISSN
  • 1071-7544 (ISSN-L)
  • 1521-0464
DOI
10.1080/10717544.2018.1494226
PMC
PMC6127843
OpenAlex
W2889706401
Cited by
127
References
35
Citations by year
2026: 5 · 2025: 16 · 2024: 20 · 2023: 14 · 2022: 25 · 2021: 27 · 2020: 10 · 2019: 10
FWCI
3.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Drug Delivery (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • ResearchSpace (University of Auckland) (submittedVersion, cc-by)
Funders
Natural Science Foundation of Shandong Province (LH076, HB58)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
Keywords
glioblastoma, nose-to-brain delivery, temozolomide, PLGA nanoparticles, targeted drug delivery, brain tumor therapy, tumor cell apoptosis
MeSH terms
Temozolomide, Animals, Antibodies, Monoclonal, Antineoplastic Agents, Brain Neoplasms, Drug Carriers, Glioblastoma, Humans, Male, Polyglactin 910, Rats, Sprague-Dawley, Receptor Protein-Tyrosine Kinases, Receptor, EphA3, Cell Line, Tumor, Rats, Nanoparticles, Molecular Targeted Therapy

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