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

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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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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.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.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.CC BY · PubMed Central

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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: Wang, Aiping
Ni, Ling
Yan, Xiuju
Song, Yina
Sun, Kaoxiang
Liu, Sha
Wu, Zimei
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: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
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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Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting

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