WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma

The global incidence of melanoma is increasing. Mortality from melanoma is influenced primarily by metastasis in advanced stages of the disease. Current treatments are largely ineffective; thus, novel gene delivery approaches that target tumor‑specific markers may be useful for the treatment of mel...

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Autores principales: Saavedra Alonso, Santiago, Zapata Benavides, Pablo, Chávez Escamilla, Ana Karina, Manilla Muñoz, Edgar, Zamora Ávila, Diana Elisa, Franco Molina, Moisés Armides, Rodríguez Padilla, Cristina
Formato: Artículo
Lenguaje:inglés
Publicado: Spandidos Publications 2016
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Acceso en línea:http://eprints.uanl.mx/28163/1/722.pdf
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author Saavedra Alonso, Santiago
Zapata Benavides, Pablo
Chávez Escamilla, Ana Karina
Manilla Muñoz, Edgar
Zamora Ávila, Diana Elisa
Franco Molina, Moisés Armides
Rodríguez Padilla, Cristina
author_facet Saavedra Alonso, Santiago
Zapata Benavides, Pablo
Chávez Escamilla, Ana Karina
Manilla Muñoz, Edgar
Zamora Ávila, Diana Elisa
Franco Molina, Moisés Armides
Rodríguez Padilla, Cristina
author_sort Saavedra Alonso, Santiago
collection Repositorio Institucional
description The global incidence of melanoma is increasing. Mortality from melanoma is influenced primarily by metastasis in advanced stages of the disease. Current treatments are largely ineffective; thus, novel gene delivery approaches that target tumor‑specific markers may be useful for the treatment of melanoma. Systemic administration of encapsulated RNA‑interference plasmids targeted against tumor cells is a potential alternative therapy for cancer. Formulations of transferrin (Tf)‑conjugated polyethylene glycol (PEG) liposomes loaded with short hairpin RNA (shRNA) against WT1 (Lip + RNAi + Tf), PEG liposomes loaded with shRNA against WT1 (Lip + RNAi), Tf‑conjugated PEG liposomes loaded with pEGFP‑N3 (Lip + GFP + Tf) and saline solution as negative control (untreated) were administered systemically to C57BL/6 mice implanted subcutaneously with a melanoma cell line. Tumor volume, body weight, tumor weight, survival and relative expression of WT1 were evaluated. No significant differences in net body weight were identified between groups. The tumor volume decreased from 7,871 mm3 (SD±2,087) in the untreated group to 5,981 mm3 (SD±2,099) in the Lip + RNAi + Tf group. The tumor weight was reduced, from 8.8 g (SD±0.30) in the untreated group to 5.5 g (SD±0.87) in the Lip + RNAi + Tf group. An increase of 37% in survival was also observed in the group treated with Lip + RNAi + Tf in comparison to the untreated group. Tumors treated with Lip + RNAi + Tf also showed a decrease in the mean relative expression of WT1 of 0.21 (SD±0.28) folds compared with 1.8 (SD±2.49) folds in untreated group, 1.34 (SD±0.43) folds in Lip + RNAi group and of 1.89 (SD±0.69) folds in Lip + GFP + Tf group. Systemic administration of transferrin‑conjugated PEG liposomes loaded with shRNA against WT1 reduced WT1 expression and tumor size and increased survival.
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spelling eprints-281632024-10-04T19:49:14Z http://eprints.uanl.mx/28163/ WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma Saavedra Alonso, Santiago Zapata Benavides, Pablo Chávez Escamilla, Ana Karina Manilla Muñoz, Edgar Zamora Ávila, Diana Elisa Franco Molina, Moisés Armides Rodríguez Padilla, Cristina QR Microbiología The global incidence of melanoma is increasing. Mortality from melanoma is influenced primarily by metastasis in advanced stages of the disease. Current treatments are largely ineffective; thus, novel gene delivery approaches that target tumor‑specific markers may be useful for the treatment of melanoma. Systemic administration of encapsulated RNA‑interference plasmids targeted against tumor cells is a potential alternative therapy for cancer. Formulations of transferrin (Tf)‑conjugated polyethylene glycol (PEG) liposomes loaded with short hairpin RNA (shRNA) against WT1 (Lip + RNAi + Tf), PEG liposomes loaded with shRNA against WT1 (Lip + RNAi), Tf‑conjugated PEG liposomes loaded with pEGFP‑N3 (Lip + GFP + Tf) and saline solution as negative control (untreated) were administered systemically to C57BL/6 mice implanted subcutaneously with a melanoma cell line. Tumor volume, body weight, tumor weight, survival and relative expression of WT1 were evaluated. No significant differences in net body weight were identified between groups. The tumor volume decreased from 7,871 mm3 (SD±2,087) in the untreated group to 5,981 mm3 (SD±2,099) in the Lip + RNAi + Tf group. The tumor weight was reduced, from 8.8 g (SD±0.30) in the untreated group to 5.5 g (SD±0.87) in the Lip + RNAi + Tf group. An increase of 37% in survival was also observed in the group treated with Lip + RNAi + Tf in comparison to the untreated group. Tumors treated with Lip + RNAi + Tf also showed a decrease in the mean relative expression of WT1 of 0.21 (SD±0.28) folds compared with 1.8 (SD±2.49) folds in untreated group, 1.34 (SD±0.43) folds in Lip + RNAi group and of 1.89 (SD±0.69) folds in Lip + GFP + Tf group. Systemic administration of transferrin‑conjugated PEG liposomes loaded with shRNA against WT1 reduced WT1 expression and tumor size and increased survival. Spandidos Publications 2016 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/28163/1/722.pdf http://eprints.uanl.mx/28163/1.haspreviewThumbnailVersion/722.pdf Saavedra Alonso, Santiago y Zapata Benavides, Pablo y Chávez Escamilla, Ana Karina y Manilla Muñoz, Edgar y Zamora Ávila, Diana Elisa y Franco Molina, Moisés Armides y Rodríguez Padilla, Cristina (2016) WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma. Experimental and Therapeutic Medicine, 12 (6). pp. 3778-3784. ISSN 1792-0981 http://doi.org/10.3892/etm.2016.3851 doi:10.3892/etm.2016.3851
spellingShingle QR Microbiología
Saavedra Alonso, Santiago
Zapata Benavides, Pablo
Chávez Escamilla, Ana Karina
Manilla Muñoz, Edgar
Zamora Ávila, Diana Elisa
Franco Molina, Moisés Armides
Rodríguez Padilla, Cristina
WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma
title_full WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma
title_fullStr WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma
title_full_unstemmed WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma
title_short WT1 shRNA delivery using transferrin-conjugated PEG liposomes in an in vivo model of melanoma
title_sort wt1 shrna delivery using transferrin conjugated peg liposomes in an in vivo model of melanoma
topic QR Microbiología
url http://eprints.uanl.mx/28163/1/722.pdf
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