Cargando…
Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma
INTRODUCTION: Cancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) among the most common cancers in both species. Comparative medicine has the potential to accelerate...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498770/ https://www.ncbi.nlm.nih.gov/pubmed/37711439 http://dx.doi.org/10.3389/fvets.2023.1236136 |
_version_ | 1785105589666316288 |
---|---|
author | André, Ana S. Dias, Joana N. R. Aguiar, Sandra I. Leonardo, Ana Nogueira, Sara Amaral, Joana D. Fernandes, Célia Gano, Lurdes Correia, João D. G. Cavaco, Marco Neves, Vera Correia, Jorge Castanho, Miguel Rodrigues, Cecília M. P. Gaspar, Maria Manuela Tavares, Luís Aires-da-Silva, Frederico |
author_facet | André, Ana S. Dias, Joana N. R. Aguiar, Sandra I. Leonardo, Ana Nogueira, Sara Amaral, Joana D. Fernandes, Célia Gano, Lurdes Correia, João D. G. Cavaco, Marco Neves, Vera Correia, Jorge Castanho, Miguel Rodrigues, Cecília M. P. Gaspar, Maria Manuela Tavares, Luís Aires-da-Silva, Frederico |
author_sort | André, Ana S. |
collection | PubMed |
description | INTRODUCTION: Cancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) among the most common cancers in both species. Comparative medicine has the potential to accelerate the development of new therapeutic options in oncology by leveraging commonalities between diseases affecting both humans and animals. Within this context, in the present study, we investigated the potential of panobinostat (Pan)-loaded folate-targeted PEGylated liposomes (FA-PEG-Pan-Lip) for the treatment of canine B-cell lymphoma, while contributing to new perspectives in comparative oncology. METHODS AND RESULTS: Two formulations were developed, namely: PEG-Pan-Lip and FA-PEG-Pan-Lip. Firstly, folate receptor expression in the CLBL-1 canine B-cell lymphoma cell line was assessed. After confirming receptor expression, both Pan-loaded formulations (PEG-Pan-Lip, FA-PEG-Pan-Lip) demonstrated dose-dependent inhibitory effects on CLBL-1 cell proliferation. The FA-PEG-Pan-Lip formulation (IC(50) = 10.9 ± 0.03 nM) showed higher cytotoxicity than the non-targeted PEG-Pan-Lip formulation (IC(50) = 12.9 ± 0.03 nM) and the free panobinostat (Pan) compound (IC(50) = 18.32±0.03 nM). Moreover, mechanistically, both Pan-containing formulations induced acetylation of H3 histone and apoptosis. Flow cytometry and immunofluorescence analysis of intracellular uptake of rhodamine-labeled liposome formulations in CLBL-1 cells confirmed cellular internalization of PEG-Lip and FA-PEG-Lip formulations and higher uptake profile for the latter. Biodistribution studies of both radiolabeled formulations in CD1 and SCID mice revealed a rapid clearance from the major organs and a 1.6-fold enhancement of tumor uptake at 24 h for (111)In-FA-PEG-Pan-Lip (2.2 ± 0.1 %ID/g of tumor) compared to (111)In-PEG-Pan-Lip formulation (1.2±0.2 %ID/g of tumor). DISCUSSION: In summary, our results provide new data validating Pan-loaded folate liposomes as a promising targeted drug delivery system for the treatment of canine B-cell lymphoma and open innovative perspectives for comparative oncology. |
format | Online Article Text |
id | pubmed-10498770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104987702023-09-14 Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma André, Ana S. Dias, Joana N. R. Aguiar, Sandra I. Leonardo, Ana Nogueira, Sara Amaral, Joana D. Fernandes, Célia Gano, Lurdes Correia, João D. G. Cavaco, Marco Neves, Vera Correia, Jorge Castanho, Miguel Rodrigues, Cecília M. P. Gaspar, Maria Manuela Tavares, Luís Aires-da-Silva, Frederico Front Vet Sci Veterinary Science INTRODUCTION: Cancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) among the most common cancers in both species. Comparative medicine has the potential to accelerate the development of new therapeutic options in oncology by leveraging commonalities between diseases affecting both humans and animals. Within this context, in the present study, we investigated the potential of panobinostat (Pan)-loaded folate-targeted PEGylated liposomes (FA-PEG-Pan-Lip) for the treatment of canine B-cell lymphoma, while contributing to new perspectives in comparative oncology. METHODS AND RESULTS: Two formulations were developed, namely: PEG-Pan-Lip and FA-PEG-Pan-Lip. Firstly, folate receptor expression in the CLBL-1 canine B-cell lymphoma cell line was assessed. After confirming receptor expression, both Pan-loaded formulations (PEG-Pan-Lip, FA-PEG-Pan-Lip) demonstrated dose-dependent inhibitory effects on CLBL-1 cell proliferation. The FA-PEG-Pan-Lip formulation (IC(50) = 10.9 ± 0.03 nM) showed higher cytotoxicity than the non-targeted PEG-Pan-Lip formulation (IC(50) = 12.9 ± 0.03 nM) and the free panobinostat (Pan) compound (IC(50) = 18.32±0.03 nM). Moreover, mechanistically, both Pan-containing formulations induced acetylation of H3 histone and apoptosis. Flow cytometry and immunofluorescence analysis of intracellular uptake of rhodamine-labeled liposome formulations in CLBL-1 cells confirmed cellular internalization of PEG-Lip and FA-PEG-Lip formulations and higher uptake profile for the latter. Biodistribution studies of both radiolabeled formulations in CD1 and SCID mice revealed a rapid clearance from the major organs and a 1.6-fold enhancement of tumor uptake at 24 h for (111)In-FA-PEG-Pan-Lip (2.2 ± 0.1 %ID/g of tumor) compared to (111)In-PEG-Pan-Lip formulation (1.2±0.2 %ID/g of tumor). DISCUSSION: In summary, our results provide new data validating Pan-loaded folate liposomes as a promising targeted drug delivery system for the treatment of canine B-cell lymphoma and open innovative perspectives for comparative oncology. Frontiers Media S.A. 2023-08-30 /pmc/articles/PMC10498770/ /pubmed/37711439 http://dx.doi.org/10.3389/fvets.2023.1236136 Text en Copyright © 2023 André, Dias, Aguiar, Leonardo, Nogueira, Amaral, Fernandes, Gano, Correia, Cavaco, Neves, Correia, Castanho, Rodrigues, Gaspar, Tavares and Aires-da-Silva. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Veterinary Science André, Ana S. Dias, Joana N. R. Aguiar, Sandra I. Leonardo, Ana Nogueira, Sara Amaral, Joana D. Fernandes, Célia Gano, Lurdes Correia, João D. G. Cavaco, Marco Neves, Vera Correia, Jorge Castanho, Miguel Rodrigues, Cecília M. P. Gaspar, Maria Manuela Tavares, Luís Aires-da-Silva, Frederico Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma |
title | Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma |
title_full | Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma |
title_fullStr | Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma |
title_full_unstemmed | Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma |
title_short | Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma |
title_sort | panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine b-cell lymphoma |
topic | Veterinary Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498770/ https://www.ncbi.nlm.nih.gov/pubmed/37711439 http://dx.doi.org/10.3389/fvets.2023.1236136 |
work_keys_str_mv | AT andreanas panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT diasjoananr panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT aguiarsandrai panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT leonardoana panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT nogueirasara panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT amaraljoanad panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT fernandescelia panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT ganolurdes panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT correiajoaodg panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT cavacomarco panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT nevesvera panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT correiajorge panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT castanhomiguel panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT rodriguesceciliamp panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT gasparmariamanuela panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT tavaresluis panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma AT airesdasilvafrederico panobinostatloadedfolatetargetedliposomesasapromisingdrugdeliverysystemfortreatmentofcaninebcelllymphoma |