Folate-Targeted Nanocarriers Co-Deliver Ganciclovir and miR-34a-5p for Combined Anti-KSHV Therapy
Kaposi's sarcoma-associated herpesvirus (KSHV) can cause a variety of malignancies. Ganciclovir (GCV) is one of the most efficient drugs against KSHV, but its non-specificity can cause other side effects in patients. Nucleic acid miR-34a-5p can inhibit the transcription of KSHV RNA and has great potential in anti-KSHV therapy, but there are still problems such as easy degradation and low delivery efficiency. Here, we constructed a co-loaded dual-drug nanocomplex (GCVZIF-8/PEI-FA+miR-34a-5p) that contains GCV internally and adsorbs miR-34a-5p externally. The folic acid (FA)-coupled polyethyleneimine (PEI) coating layer (PEI-FA) was shown to increase the cellular uptake of the nanocomplex, which is conducive to the enrichment of drugs at the KSHV infection site. GCV and miR-34a-5p are released at the site of the KSHV infection through the acid hydrolysis characteristics of ZIF-8 and the "proton sponge effect" of PEI. The co-loaded dual-drug nanocomplex not only inhibits the proliferation and migration of KSHV-positive cells but also decreases the mRNA expression level of KSHV lytic and latent genes. In conclusion, this co-loaded dual-drug nanocomplex may provide an attractive strategy for antiviral drug delivery and anti-KSHV therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
International journal of molecular sciences - 25(2024), 5 vom: 02. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Fangling [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-KSHV therapy |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 15.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms25052932 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369638999 |
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| 520 | |a Kaposi's sarcoma-associated herpesvirus (KSHV) can cause a variety of malignancies. Ganciclovir (GCV) is one of the most efficient drugs against KSHV, but its non-specificity can cause other side effects in patients. Nucleic acid miR-34a-5p can inhibit the transcription of KSHV RNA and has great potential in anti-KSHV therapy, but there are still problems such as easy degradation and low delivery efficiency. Here, we constructed a co-loaded dual-drug nanocomplex (GCVZIF-8/PEI-FA+miR-34a-5p) that contains GCV internally and adsorbs miR-34a-5p externally. The folic acid (FA)-coupled polyethyleneimine (PEI) coating layer (PEI-FA) was shown to increase the cellular uptake of the nanocomplex, which is conducive to the enrichment of drugs at the KSHV infection site. GCV and miR-34a-5p are released at the site of the KSHV infection through the acid hydrolysis characteristics of ZIF-8 and the "proton sponge effect" of PEI. The co-loaded dual-drug nanocomplex not only inhibits the proliferation and migration of KSHV-positive cells but also decreases the mRNA expression level of KSHV lytic and latent genes. In conclusion, this co-loaded dual-drug nanocomplex may provide an attractive strategy for antiviral drug delivery and anti-KSHV therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a anti-KSHV therapy | |
| 650 | 4 | |a co-loaded dual-drug nanocomplex | |
| 650 | 4 | |a combination of two drugs | |
| 650 | 4 | |a ganciclovir | |
| 650 | 4 | |a miR-34a-5p | |
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| 650 | 7 | |a MicroRNAs |2 NLM | |
| 700 | 1 | |a Cao, Dongdong |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Wenyi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Dongmei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Lin |e verfasserin |4 aut | |
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