Academic Journal
Dual-Peptide PAMAM Dendrimer Conjugates for Enhanced Cell Uptake via E-Selectin Targeting.
| Τίτλος: | Dual-Peptide PAMAM Dendrimer Conjugates for Enhanced Cell Uptake via E-Selectin Targeting. |
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| Συγγραφείς: | Marrugo KP; Facultad de Ciencias Químicas, Universidad de Concepción, Edmundo Larenas 129, Concepción 4030000, Chile., Manzo-Merino J; Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico., Jiménez VA; Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Autopista Concepción-Talcahuano 7100, Talcahuano 4260000, Chile., Campos CH; Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Autopista Concepción-Talcahuano 7100, Talcahuano 4260000, Chile., Alderete JB; Instituto de Química de Recursos Naturales (IQRN), Universidad de Talca, Avenida Lircay S/N, Casilla 747, Talca 3460000, Chile. |
| Πηγή: | Bioconjugate chemistry [Bioconjug Chem] 2025 Dec 17; Vol. 36 (12), pp. 2608-2617. Date of Electronic Publication: 2025 Nov 21. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9010319 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4812 (Electronic) Linking ISSN: 10431802 NLM ISO Abbreviation: Bioconjug Chem Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Chemical Society, c1990- |
| Ιατρικοί όροι (MeSH): | Dendrimers*/chemistry , Dendrimers*/metabolism , E-Selectin*/metabolism , Peptides*/chemistry , Peptides*/metabolism , Drug Carriers*/chemistry , Drug Carriers*/metabolism, Doxorubicin/pharmacology ; Humans ; Human Umbilical Vein Endothelial Cells ; Cell Line, Tumor |
| Περίληψη: | E-selectin is a highly glycosylated protein overexpressed on the surface of endothelial cells within the tumor vasculature, especially at sites of active angiogenesis and metastasis. This localized overexpression raises the opportunity to target the tumor microenvironment by using nanocarriers capable of specific recognition by this protein. In this work, we report dual-peptide PAMAM dendrimer conjugates as novel nanocarriers with specific E-selectin-mediated uptake properties. The conjugates were obtained from fourth-generation PAMAM dendrimers that were partially acetylated and doubly conjugated with an E-selectin targeting peptide (CIELLQAR or CIELFQAR) and the cell-penetrating peptide pTAT. Acetylation degrees close to 50% were successfully achieved, with peptide substitution ratios corresponding to 3-4 pTAT units and 2-3 E-selectin targeting peptides per dendrimer, as determined from NMR analysis. The dual-peptide conjugated dendrimers showed excellent safety profiles, with negligible intrinsic cytotoxicity in HUVEC/TERT2 and T98G cells, as models for endothelial and tumor cells. Their E-selectin-mediated uptake was confirmed in endothelial cells overexpressing E-selectin and blocked in cells treated with an anti-E-selectin antibody, with the pTAT-CIELFQAR-conjugated dendrimer having a superior performance. The best dual-peptide dendrimer conjugate was also internalized by T98G cells, which was attributed to the pTAT cell internalization properties. In preliminary assays, this system proved capable of delivering doxorubicin to tumor cells, which highlights the potential of this functional dendrimer conjugate as a novel platform for targeted cancer therapy. |
| Substance Nomenclature: | 0 (Dendrimers) 0 (E-Selectin) 0 (PAMAM Starburst) 0 (Peptides) 80168379AG (Doxorubicin) 0 (Drug Carriers) |
| Entry Date(s): | Date Created: 20251121 Date Completed: 20251217 Latest Revision: 20260518 |
| Update Code: | 20260518 |
| DOI: | 10.1021/acs.bioconjchem.5c00443 |
| PMID: | 41269873 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1520-4812 |
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| DOI: | 10.1021/acs.bioconjchem.5c00443 |