Fluorinated Cell-Penetrating Peptide for Co-Delivering siHIF-1α and Sorafenib to Enhance In Vitro Anti-Tumor Efficacy
Antiangiogenic therapy with sorafenib (SF) alone is ineffective in eradicating tumors, and its long-term application can exacerbate tumor hypoxia, which in turn restricts SF's therapeutic efficacy. Here, a redox-responsive fluorinated peptide (DEN-TAT-PFC) consisting of dendritic poly-lysine, cell-penetrating peptide TAT, and perfluorocarbon was designed and synthesized to co-load siRNA-targeting hypoxia-inducible factors (siHIF-1α) and SF. The unique architecture of the peptide and fluorinated modifications enhanced the siRNA delivery efficiency, including increased siRNA binding, GSH-responsive release, cellular uptake, endosomal escape, and serum resistance. Simultaneously, the DEN-TAT-PFC/SF/siHIF-1α co-delivery system achieved efficient knockdown of HIF-1α at mRNA and protein levels, thus alleviating hypoxia and further substantially reducing VEGF expression. Additionally, the excellent oxygen-carrying ability of DEN-TAT-PFC may facilitate relief of the hypoxic microenvironment. As a result of these synergistic effects, DEN-TAT-PFC/SF/siHIF-1α exhibited considerable anti-tumor cell proliferation and anti-angiogenesis effects. Therefore, DEN-TAT-PFC can be a versatile platform for fabricating fluorine-containing drugs/siRNA complex nano-systems.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Pharmaceutics - 15(2023), 12 vom: 16. Dez. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wan, Yu [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 25.12.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/pharmaceutics15122789 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366307878 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366307878 | ||
| 003 | DE-627 | ||
| 005 | 20231227141150.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231227s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/pharmaceutics15122789 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1238.xml |
| 035 | |a (DE-627)NLM366307878 | ||
| 035 | |a (NLM)38140129 | ||
| 035 | |a (PII)2789 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wan, Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Fluorinated Cell-Penetrating Peptide for Co-Delivering siHIF-1α and Sorafenib to Enhance In Vitro Anti-Tumor Efficacy |
| 264 | 1 | |c 2023 | |
| 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 Revised 25.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Antiangiogenic therapy with sorafenib (SF) alone is ineffective in eradicating tumors, and its long-term application can exacerbate tumor hypoxia, which in turn restricts SF's therapeutic efficacy. Here, a redox-responsive fluorinated peptide (DEN-TAT-PFC) consisting of dendritic poly-lysine, cell-penetrating peptide TAT, and perfluorocarbon was designed and synthesized to co-load siRNA-targeting hypoxia-inducible factors (siHIF-1α) and SF. The unique architecture of the peptide and fluorinated modifications enhanced the siRNA delivery efficiency, including increased siRNA binding, GSH-responsive release, cellular uptake, endosomal escape, and serum resistance. Simultaneously, the DEN-TAT-PFC/SF/siHIF-1α co-delivery system achieved efficient knockdown of HIF-1α at mRNA and protein levels, thus alleviating hypoxia and further substantially reducing VEGF expression. Additionally, the excellent oxygen-carrying ability of DEN-TAT-PFC may facilitate relief of the hypoxic microenvironment. As a result of these synergistic effects, DEN-TAT-PFC/SF/siHIF-1α exhibited considerable anti-tumor cell proliferation and anti-angiogenesis effects. Therefore, DEN-TAT-PFC can be a versatile platform for fabricating fluorine-containing drugs/siRNA complex nano-systems | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a fluorination | |
| 650 | 4 | |a hypoxia | |
| 650 | 4 | |a peptide | |
| 650 | 4 | |a siRNA delivery | |
| 700 | 1 | |a Yang, Yuhan |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Qiuyue |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wangxia |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Mingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Shun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmaceutics |d 2010 |g 15(2023), 12 vom: 16. Dez. |w (DE-627)NLM204303303 |x 1999-4923 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2023 |g number:12 |g day:16 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/pharmaceutics15122789 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2023 |e 12 |b 16 |c 12 | ||