Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells

Miaozhong Ni,1,* Min Xiong,1,* Xinchao Zhang,1,* Guoping Cai,1 Huaiwen Chen,2 Qingmin Zeng,1 Zuochong Yu1 1Department of Orthopedics, Jinshan Hospital, Fudan University, 2International Joint Cancer Institute, the Second Military Medical University, Shanghai, People’s Republic of China *...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ni MZ, Xiong M, Zhang XC, Cai GP, Chen HW, Zeng QM, Yu ZC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d20a923729cc4e0ca95d1cc0cf62efe2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d20a923729cc4e0ca95d1cc0cf62efe2
record_format	dspace
spelling	oai:doaj.org-article:d20a923729cc4e0ca95d1cc0cf62efe22021-12-02T05:10:45ZPoly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells1178-2013https://doaj.org/article/d20a923729cc4e0ca95d1cc0cf62efe22015-03-01T00:00:00Zhttp://www.dovepress.com/polylactic-co-glycolic-acid-nanoparticles-conjugated-with-cd133-aptame-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Miaozhong Ni,1,* Min Xiong,1,* Xinchao Zhang,1,* Guoping Cai,1 Huaiwen Chen,2 Qingmin Zeng,1 Zuochong Yu1 1Department of Orthopedics, Jinshan Hospital, Fudan University, 2International Joint Cancer Institute, the Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Cancer stem cells (CSCs) possess the characteristics associated with normal stem cells and are responsible for cancer initiation, recurrence, and metastasis. CD133 is regarded as a CSCs marker of osteosarcoma, which is the most common primary bone malignancy in childhood and adolescence. Salinomycin, a polyether ionophore antibiotic, has been shown to kill various CSCs, including osteosarcoma CSCs. However, salinomycin displayed poor aqueous solubility that hinders its clinical application. The objective of this study was to develop salinomycin-loaded nanoparticles to eliminate CD133+ osteosarcoma CSCs.Methods: The salinomycin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles (SAL-NP) conjugated with CD133 aptamers (Ap-SAL-NP) were developed by an emulsion/solvent evaporation method, and the targeting and cytotoxicity of Ap-SAL-NP to CD133+ osteosarcoma CSCs were evaluated.Results: The nanoparticles are of desired particle size (~150 nm), drug encapsulation efficiency (~50%), and drug release profile. After 48 hours treatment of the Saos-2 CD133+ osteosarcoma cells with drugs formulated in Ap-SAL-NP, SAL-NP, and salinomycin, the concentrations needed to kill 50% of the incubated cells were found to be 2.18, 10.72, and 5.07 µg/mL, respectively, suggesting that Ap-SAL-NP could be 4.92 or 2.33 fold more effective than SAL-NP or salinomycin, respectively. In contrast, Ap-SAL-NP was as effective as SAL-NP, and less effective than salinomycin in Saos-2 CD133- cells, suggesting that Ap-SAL-NP possess specific cytotoxicity toward Saos-2 CD133+ cells. Ap-SAL-NP showed the best therapeutic effect in Saos-2 osteosarcoma xenograft mice, compared with SAL-NP or salinomycin. Significantly, Ap-SAL-NP could selectively kill CD133+ osteosarcoma CSCs both in vitro and in vivo, as reflected by the tumorsphere formation and proportion of Saos-2 CD133+ cells.Conclusion: Our results suggest that CD133 is a potential target for drug delivery to osteosarcoma CSCs and that it is possible to significantly inhibit the osteosarcoma growth by killing CD133+ osteosarcoma CSCs. We demonstrated that Ap-SAL-NP have the potential to target and kill CD133+ osteosarcoma CSCs. Keywords: targeted therapy, ligand-conjugated nanomedicines, cancer initiating cellsNi MZXiong MZhang XCCai GPChen HWZeng QMYu ZCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2537-2554 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Ni MZ Xiong M Zhang XC Cai GP Chen HW Zeng QM Yu ZC Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells
description	Miaozhong Ni,1,* Min Xiong,1,* Xinchao Zhang,1,* Guoping Cai,1 Huaiwen Chen,2 Qingmin Zeng,1 Zuochong Yu1 1Department of Orthopedics, Jinshan Hospital, Fudan University, 2International Joint Cancer Institute, the Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Cancer stem cells (CSCs) possess the characteristics associated with normal stem cells and are responsible for cancer initiation, recurrence, and metastasis. CD133 is regarded as a CSCs marker of osteosarcoma, which is the most common primary bone malignancy in childhood and adolescence. Salinomycin, a polyether ionophore antibiotic, has been shown to kill various CSCs, including osteosarcoma CSCs. However, salinomycin displayed poor aqueous solubility that hinders its clinical application. The objective of this study was to develop salinomycin-loaded nanoparticles to eliminate CD133+ osteosarcoma CSCs.Methods: The salinomycin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles (SAL-NP) conjugated with CD133 aptamers (Ap-SAL-NP) were developed by an emulsion/solvent evaporation method, and the targeting and cytotoxicity of Ap-SAL-NP to CD133+ osteosarcoma CSCs were evaluated.Results: The nanoparticles are of desired particle size (~150 nm), drug encapsulation efficiency (~50%), and drug release profile. After 48 hours treatment of the Saos-2 CD133+ osteosarcoma cells with drugs formulated in Ap-SAL-NP, SAL-NP, and salinomycin, the concentrations needed to kill 50% of the incubated cells were found to be 2.18, 10.72, and 5.07 µg/mL, respectively, suggesting that Ap-SAL-NP could be 4.92 or 2.33 fold more effective than SAL-NP or salinomycin, respectively. In contrast, Ap-SAL-NP was as effective as SAL-NP, and less effective than salinomycin in Saos-2 CD133- cells, suggesting that Ap-SAL-NP possess specific cytotoxicity toward Saos-2 CD133+ cells. Ap-SAL-NP showed the best therapeutic effect in Saos-2 osteosarcoma xenograft mice, compared with SAL-NP or salinomycin. Significantly, Ap-SAL-NP could selectively kill CD133+ osteosarcoma CSCs both in vitro and in vivo, as reflected by the tumorsphere formation and proportion of Saos-2 CD133+ cells.Conclusion: Our results suggest that CD133 is a potential target for drug delivery to osteosarcoma CSCs and that it is possible to significantly inhibit the osteosarcoma growth by killing CD133+ osteosarcoma CSCs. We demonstrated that Ap-SAL-NP have the potential to target and kill CD133+ osteosarcoma CSCs. Keywords: targeted therapy, ligand-conjugated nanomedicines, cancer initiating cells
format	article
author	Ni MZ Xiong M Zhang XC Cai GP Chen HW Zeng QM Yu ZC
author_facet	Ni MZ Xiong M Zhang XC Cai GP Chen HW Zeng QM Yu ZC
author_sort	Ni MZ
title	Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells
title_short	Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells
title_full	Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells
title_fullStr	Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells
title_full_unstemmed	Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells
title_sort	poly(lactic-co-glycolic acid) nanoparticles conjugated with cd133 aptamers for targeted salinomycin delivery to cd133+ osteosarcoma cancer stem cells
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/d20a923729cc4e0ca95d1cc0cf62efe2
work_keys_str_mv	AT nimz polylacticcoglycolicacidnanoparticlesconjugatedwithcd133aptamersfortargetedsalinomycindeliverytocd133osteosarcomacancerstemcells AT xiongm polylacticcoglycolicacidnanoparticlesconjugatedwithcd133aptamersfortargetedsalinomycindeliverytocd133osteosarcomacancerstemcells AT zhangxc polylacticcoglycolicacidnanoparticlesconjugatedwithcd133aptamersfortargetedsalinomycindeliverytocd133osteosarcomacancerstemcells AT caigp polylacticcoglycolicacidnanoparticlesconjugatedwithcd133aptamersfortargetedsalinomycindeliverytocd133osteosarcomacancerstemcells AT chenhw polylacticcoglycolicacidnanoparticlesconjugatedwithcd133aptamersfortargetedsalinomycindeliverytocd133osteosarcomacancerstemcells AT zengqm polylacticcoglycolicacidnanoparticlesconjugatedwithcd133aptamersfortargetedsalinomycindeliverytocd133osteosarcomacancerstemcells AT yuzc polylacticcoglycolicacidnanoparticlesconjugatedwithcd133aptamersfortargetedsalinomycindeliverytocd133osteosarcomacancerstemcells
_version_	1718400562026774528

Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells

Ejemplares similares