Topical Application of Cell-Penetrating Peptide Modified Anti-VEGF Drug Alleviated Choroidal Neovascularization in Mice
© 2024 Hu et al..
Background: Age-related macular degeneration (AMD) stands as the foremost cause of irreversible central vision impairment, marked by choroidal neovascularization (CNV). The prevailing clinical approach to AMD treatment relies on intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, this method is encumbered by diverse complications, prompting exploration of non-invasive alternatives such as ocular administration via eye drops for anti-VEGF therapy.
Methods: Two complexes, 5-FITC-CPP-Ranibizumab (5-FCR) and 5-FITC-CPP-Conbercept (5-FCC), were synthesized by incorporating the anti-VEGF drugs Ranibizumab (RBZ) or Conbercept (CBC) with cell-penetrating peptide (CPP). Circular dichroism spectrum (CD) facilitated complexes characterization. Eye drops was utilized to address laser-induced CNV in mice. Fluorescein fundus angiography (FFA) observe the CNV lesion, while FITC-dextran and IB4 dual fluorescent staining, along with hematoxylin-eosin (HE) staining, assessed in lesion size. Tissue immunofluorescence examined CD31 and VEGF expression in choroidal/retinal pigment epithelial (RPE) tissues. Biocompatibility and biosafety of 5-FCR and 5-FCC was evaluated through histological examination of various organs or cell experiments.
Results: Both 5-FCR and 5-FCC exhibited favorable biocompatibility and safety profiles. VEGF-induced migration of Human umbilical vein endothelial cells (HUVECs) significantly decreased post-5-FCR/5-FCC treatment. Additionally, both complexes suppressed VEGF-induced tube formation in HUVECs. FFA results revealed a significant improvement in retinal exudation in mice. Histological examination unveiled the lesion areas in the 5-FCR and 5-FCC groups showed a significant reduction compared to the control group. Similar outcomes were observed in histological sections of the RPE-choroid-sclera flat mounts.
Conclusion: In this study, utilizing the properties of CPP and two anti-VEGF drugs, we successfully synthesized two complexes, 5-FCR and 5-FCC, through a straightforward approach. Effectively delivering the anti-VEGF drugs to the target area in a non-invasive manner, suppressing the progression of laser-induced CNV. This offers a novel approach for the treatment of wet AMD.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
International journal of nanomedicine - 19(2024) vom: 14., Seite 35-51 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hu, Weinan [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 09.01.2024 Date Revised 09.01.2024 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.2147/IJN.S428684 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366785249 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366785249 | ||
| 003 | DE-627 | ||
| 005 | 20240114233149.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240114s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2147/IJN.S428684 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1253.xml |
| 035 | |a (DE-627)NLM366785249 | ||
| 035 | |a (NLM)38187905 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hu, Weinan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Topical Application of Cell-Penetrating Peptide Modified Anti-VEGF Drug Alleviated Choroidal Neovascularization in Mice |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.01.2024 | ||
| 500 | |a Date Revised 09.01.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 Hu et al. | ||
| 520 | |a Background: Age-related macular degeneration (AMD) stands as the foremost cause of irreversible central vision impairment, marked by choroidal neovascularization (CNV). The prevailing clinical approach to AMD treatment relies on intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, this method is encumbered by diverse complications, prompting exploration of non-invasive alternatives such as ocular administration via eye drops for anti-VEGF therapy | ||
| 520 | |a Methods: Two complexes, 5-FITC-CPP-Ranibizumab (5-FCR) and 5-FITC-CPP-Conbercept (5-FCC), were synthesized by incorporating the anti-VEGF drugs Ranibizumab (RBZ) or Conbercept (CBC) with cell-penetrating peptide (CPP). Circular dichroism spectrum (CD) facilitated complexes characterization. Eye drops was utilized to address laser-induced CNV in mice. Fluorescein fundus angiography (FFA) observe the CNV lesion, while FITC-dextran and IB4 dual fluorescent staining, along with hematoxylin-eosin (HE) staining, assessed in lesion size. Tissue immunofluorescence examined CD31 and VEGF expression in choroidal/retinal pigment epithelial (RPE) tissues. Biocompatibility and biosafety of 5-FCR and 5-FCC was evaluated through histological examination of various organs or cell experiments | ||
| 520 | |a Results: Both 5-FCR and 5-FCC exhibited favorable biocompatibility and safety profiles. VEGF-induced migration of Human umbilical vein endothelial cells (HUVECs) significantly decreased post-5-FCR/5-FCC treatment. Additionally, both complexes suppressed VEGF-induced tube formation in HUVECs. FFA results revealed a significant improvement in retinal exudation in mice. Histological examination unveiled the lesion areas in the 5-FCR and 5-FCC groups showed a significant reduction compared to the control group. Similar outcomes were observed in histological sections of the RPE-choroid-sclera flat mounts | ||
| 520 | |a Conclusion: In this study, utilizing the properties of CPP and two anti-VEGF drugs, we successfully synthesized two complexes, 5-FCR and 5-FCC, through a straightforward approach. Effectively delivering the anti-VEGF drugs to the target area in a non-invasive manner, suppressing the progression of laser-induced CNV. This offers a novel approach for the treatment of wet AMD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a age-related macular degeneration | |
| 650 | 4 | |a cell-penetrating peptide | |
| 650 | 4 | |a choroidal neovascularization | |
| 650 | 4 | |a conbercept | |
| 650 | 4 | |a drug delivery | |
| 650 | 4 | |a ranibizumab | |
| 650 | 7 | |a Cell-Penetrating Peptides |2 NLM | |
| 650 | 7 | |a Fluorescein-5-isothiocyanate |2 NLM | |
| 650 | 7 | |a I223NX31W9 |2 NLM | |
| 650 | 7 | |a Ranibizumab |2 NLM | |
| 650 | 7 | |a ZL1R02VT79 |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor A |2 NLM | |
| 650 | 7 | |a Ophthalmic Solutions |2 NLM | |
| 700 | 1 | |a Cai, Wenting |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Chengda |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Donghui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Tianyi |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Ding |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jing |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of nanomedicine |d 2006 |g 19(2024) vom: 14., Seite 35-51 |w (DE-627)NLM16062035X |x 1178-2013 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2024 |g day:14 |g pages:35-51 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2147/IJN.S428684 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2024 |b 14 |h 35-51 | ||