Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids

Abstract Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluor...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bryce McCarthy, Amit Cudykier, Ravi Singh, Nicole Levi-Polyachenko, Shay Soker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/25d4a3527b974cd492f287ed093df784
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:25d4a3527b974cd492f287ed093df784
record_format	dspace
spelling	oai:doaj.org-article:25d4a3527b974cd492f287ed093df7842021-12-02T14:12:40ZSemiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids10.1038/s41598-021-81122-w2045-2322https://doaj.org/article/25d4a3527b974cd492f287ed093df7842021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81122-whttps://doaj.org/toc/2045-2322Abstract Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluorescence offer advantages for detection and treatment of disseminated small nodules. A major hurdle in clinical translation of nanoparticles is their interaction with the 3D tumor microenvironment. To address this problem tumor organoid technology was used to evaluate the ablative potential of CD44-targeted polymer nanoparticles using hyaluronic acid (HA) as the targeting agent and coating it onto hybrid donor acceptor polymer particles (HDAPPs) to form HA-HDAPPs. Additionally, nanoparticles composed from only the photothermal polymer, poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe), were also coated with HA, to form HA-BSe NPs, and evaluated in 3D. Monitoring of nanoparticle transport in 3D organoids revealed uniform diffusion of non-targeted HDAPPs in comparison to attenuated diffusion of HA-HDAPPs due to nanoparticle-matrix interactions. Computational diffusion profiles suggested that HA-HDAPPs transport may not be accounted for by diffusion alone, which is indicative of nanoparticle/cell matrix interactions. Photothermal activation revealed that only HA-BSe NPs were able to significantly reduce tumor cell viability in the organoids. Despite limited transport of the CD44-targeted theranostic nanoparticles, their targeted retention provides increased heat for enhanced photothermal ablation in 3D, which is beneficial for assessing nanoparticle therapies prior to in vivo testing.Bryce McCarthyAmit CudykierRavi SinghNicole Levi-PolyachenkoShay SokerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bryce McCarthy Amit Cudykier Ravi Singh Nicole Levi-Polyachenko Shay Soker Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids
description	Abstract Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluorescence offer advantages for detection and treatment of disseminated small nodules. A major hurdle in clinical translation of nanoparticles is their interaction with the 3D tumor microenvironment. To address this problem tumor organoid technology was used to evaluate the ablative potential of CD44-targeted polymer nanoparticles using hyaluronic acid (HA) as the targeting agent and coating it onto hybrid donor acceptor polymer particles (HDAPPs) to form HA-HDAPPs. Additionally, nanoparticles composed from only the photothermal polymer, poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe), were also coated with HA, to form HA-BSe NPs, and evaluated in 3D. Monitoring of nanoparticle transport in 3D organoids revealed uniform diffusion of non-targeted HDAPPs in comparison to attenuated diffusion of HA-HDAPPs due to nanoparticle-matrix interactions. Computational diffusion profiles suggested that HA-HDAPPs transport may not be accounted for by diffusion alone, which is indicative of nanoparticle/cell matrix interactions. Photothermal activation revealed that only HA-BSe NPs were able to significantly reduce tumor cell viability in the organoids. Despite limited transport of the CD44-targeted theranostic nanoparticles, their targeted retention provides increased heat for enhanced photothermal ablation in 3D, which is beneficial for assessing nanoparticle therapies prior to in vivo testing.
format	article
author	Bryce McCarthy Amit Cudykier Ravi Singh Nicole Levi-Polyachenko Shay Soker
author_facet	Bryce McCarthy Amit Cudykier Ravi Singh Nicole Levi-Polyachenko Shay Soker
author_sort	Bryce McCarthy
title	Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids
title_short	Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids
title_full	Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids
title_fullStr	Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids
title_full_unstemmed	Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids
title_sort	semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/25d4a3527b974cd492f287ed093df784
work_keys_str_mv	AT brycemccarthy semiconductingpolymernanoparticlesforphotothermalablationofcolorectalcancerorganoids AT amitcudykier semiconductingpolymernanoparticlesforphotothermalablationofcolorectalcancerorganoids AT ravisingh semiconductingpolymernanoparticlesforphotothermalablationofcolorectalcancerorganoids AT nicolelevipolyachenko semiconductingpolymernanoparticlesforphotothermalablationofcolorectalcancerorganoids AT shaysoker semiconductingpolymernanoparticlesforphotothermalablationofcolorectalcancerorganoids
_version_	1718391774965137408

Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids

Ejemplares similares