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Synthesis and Evaluation of (177)Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells

The peptide-receptor radionuclide therapy (PRRT) is a successful approach for selectively delivering radiation within tumor sites through specific recognition of radiolabeled peptides by overexpressed receptors on cancer cell surfaces. The efficacy of PRRT could be improved by using polymeric radio-...

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Autores principales: Gibbens-Bandala, Brenda, Morales-Avila, Enrique, Ferro-Flores, Guillermina, Santos-Cuevas, Clara, Luna-Gutiérrez, Myrna, Ramírez-Nava, Gerardo, Ocampo-García, Blanca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835492/
https://www.ncbi.nlm.nih.gov/pubmed/31569625
http://dx.doi.org/10.3390/polym11101572
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author Gibbens-Bandala, Brenda
Morales-Avila, Enrique
Ferro-Flores, Guillermina
Santos-Cuevas, Clara
Luna-Gutiérrez, Myrna
Ramírez-Nava, Gerardo
Ocampo-García, Blanca
author_facet Gibbens-Bandala, Brenda
Morales-Avila, Enrique
Ferro-Flores, Guillermina
Santos-Cuevas, Clara
Luna-Gutiérrez, Myrna
Ramírez-Nava, Gerardo
Ocampo-García, Blanca
author_sort Gibbens-Bandala, Brenda
collection PubMed
description The peptide-receptor radionuclide therapy (PRRT) is a successful approach for selectively delivering radiation within tumor sites through specific recognition of radiolabeled peptides by overexpressed receptors on cancer cell surfaces. The efficacy of PRRT could be improved by using polymeric radio- and drug- therapy nanoparticles for a concomitant therapeutic effect on malignant cells. This research aimed to prepare and evaluate, a novel drug and radiation delivery nanosystem based on the (177)Lu-labeled polyamidoamine (PAMAM) dendrimer (DN) loaded with paclitaxel (PTX) and functionalized on the surface with the Lys(1)Lys(3)(DOTA)-bombesin (BN) peptide for specific targeting to gastrin-releasing peptide receptors (GRPr) overexpressed on breast cancer cells. DN was first conjugated covalently to BN and DOTA (chemical moiety for lutetium-177 complexing) and subsequently loaded with PTX. The characterization by microscopic and spectroscopic techniques, in-vitro drug delivery tests as well as in in-vitro and in-vivo cellular uptake of (177)Lu-DOTA-DN(PTX)-BN by T47D breast cancer cells (GRPr-positive), indicated the formation of an improved delivery nanosystem with target-specific recognition by GRPr. Results of the (177)Lu-DOTA-DN(PTX)-BN effect on T47D cell viability (1.3%, compared with 10.9% of (177)Lu-DOTA-DN-BN and 14.0% of DOTA-DN-(PTX)-BN) demonstrated the concomitant radiotherapeutic and chemotherapeutic properties of the polymeric nanosystem as a potential agent for the treatment of GRPr-positive tumors.
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spelling pubmed-68354922019-11-25 Synthesis and Evaluation of (177)Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells Gibbens-Bandala, Brenda Morales-Avila, Enrique Ferro-Flores, Guillermina Santos-Cuevas, Clara Luna-Gutiérrez, Myrna Ramírez-Nava, Gerardo Ocampo-García, Blanca Polymers (Basel) Article The peptide-receptor radionuclide therapy (PRRT) is a successful approach for selectively delivering radiation within tumor sites through specific recognition of radiolabeled peptides by overexpressed receptors on cancer cell surfaces. The efficacy of PRRT could be improved by using polymeric radio- and drug- therapy nanoparticles for a concomitant therapeutic effect on malignant cells. This research aimed to prepare and evaluate, a novel drug and radiation delivery nanosystem based on the (177)Lu-labeled polyamidoamine (PAMAM) dendrimer (DN) loaded with paclitaxel (PTX) and functionalized on the surface with the Lys(1)Lys(3)(DOTA)-bombesin (BN) peptide for specific targeting to gastrin-releasing peptide receptors (GRPr) overexpressed on breast cancer cells. DN was first conjugated covalently to BN and DOTA (chemical moiety for lutetium-177 complexing) and subsequently loaded with PTX. The characterization by microscopic and spectroscopic techniques, in-vitro drug delivery tests as well as in in-vitro and in-vivo cellular uptake of (177)Lu-DOTA-DN(PTX)-BN by T47D breast cancer cells (GRPr-positive), indicated the formation of an improved delivery nanosystem with target-specific recognition by GRPr. Results of the (177)Lu-DOTA-DN(PTX)-BN effect on T47D cell viability (1.3%, compared with 10.9% of (177)Lu-DOTA-DN-BN and 14.0% of DOTA-DN-(PTX)-BN) demonstrated the concomitant radiotherapeutic and chemotherapeutic properties of the polymeric nanosystem as a potential agent for the treatment of GRPr-positive tumors. MDPI 2019-09-27 /pmc/articles/PMC6835492/ /pubmed/31569625 http://dx.doi.org/10.3390/polym11101572 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gibbens-Bandala, Brenda
Morales-Avila, Enrique
Ferro-Flores, Guillermina
Santos-Cuevas, Clara
Luna-Gutiérrez, Myrna
Ramírez-Nava, Gerardo
Ocampo-García, Blanca
Synthesis and Evaluation of (177)Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells
title Synthesis and Evaluation of (177)Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells
title_full Synthesis and Evaluation of (177)Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells
title_fullStr Synthesis and Evaluation of (177)Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells
title_full_unstemmed Synthesis and Evaluation of (177)Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells
title_short Synthesis and Evaluation of (177)Lu-DOTA-DN(PTX)-BN for Selective and Concomitant Radio and Drug—Therapeutic Effect on Breast Cancer Cells
title_sort synthesis and evaluation of (177)lu-dota-dn(ptx)-bn for selective and concomitant radio and drug—therapeutic effect on breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835492/
https://www.ncbi.nlm.nih.gov/pubmed/31569625
http://dx.doi.org/10.3390/polym11101572
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