El objetivo de este trabajo fue la preparación de un sistema nanoparticulado multifuncional que incorpora el colorante IR-780, una sonda de imagen infrarroja cercana (NIR) que presenta propiedades fototérmicas y fotodinámicas; y un derivado del succinato de α-tocoferilo (α-TOS), un compuesto anticancerígeno con acción selectiva en las mitocondrias de células tumorales. La sonda IR-780 se conjugó con el segmento hidrófilo del copolímero PEG-b-poliMTOS, sintetizado a partir de poli(etilenglicol) (PEG) y un derivado metacrílico del α-TOS (MTOS), para generar nanopartículas autoensambladas en medio acuoso con una corteza hidrofílica y un nucleo hidrofóbico, denominadas IR-NP. Durante el proceso de autoensamblado, el núcleo de IR-NP permitió encapsular IR-780 adicional para generar nanopartículas con diferente concentración de este colorante (IR-NP-eIR).
La evaluación in vitro de las propiedades fototerapeúticas de IR-NP e IR-NP-eIR se llevó a cabo minuciosamente. Así pues, las partículas desarrolladas mostraron una fluorescencia y un comportamiento fototérmico distintos después de la excitación por una luz láser que emitía a 808 nm. El tratamiento de las células MDA-MB-453 con IR-NP o IR-NP-eIR dio como resultado una internalización eficiente del colorante IR-780, mientras que la posterior irradiación con láser NIR condujo a una disminución severa en la viabilidad celular. La fototoxicidad conducida por IR-NP, que no pudo atribuirse a la generación de una hipertermia letal, produjo un aumento en los niveles de especies de oxígeno reactivo intracelular (ROS). Por lo tanto, la imagen de fluorescencia y la fototoxicidad inducida por las nanopartículas derivadas del copolímero IR-780-PEG-b-poliMTOS confieren un alto valor a estas herramientas nanoterapeúticas en la investigación clínica del cáncer.
3729048
VI52CUKS
items
1
nature
0
default
asc
1
1
title
351
http://www.biomateriales.ictp.csic.es/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-a10a765ff5b0b6da0898cda09ad4075c%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22VI52CUKS%22%2C%22library%22%3A%7B%22id%22%3A3729048%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Palao-Suay%20et%20al.%22%2C%22parsedDate%22%3A%222017-07-15%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%20style%3D%5C%22clear%3A%20left%3B%20%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-left-margin%5C%22%20style%3D%5C%22float%3A%20left%3B%20padding-right%3A%200.5em%3B%20text-align%3A%20right%3B%20width%3A%201em%3B%5C%22%3E1.%3C%5C%2Fdiv%3E%3Cdiv%20class%3D%5C%22csl-right-inline%5C%22%20style%3D%5C%22margin%3A%200%20.4em%200%201.5em%3B%5C%22%3EPalao-Suay%2C%20R.%20%3Ci%3Eet%20al.%3C%5C%2Fi%3E%20%3Ca%20target%3D%27_blank%27%20href%3D%27http%3A%5C%2F%5C%2Fwww.sciencedirect.com%5C%2Fscience%5C%2Farticle%5C%2Fpii%5C%2FS1742706117303100%27%3EPhotothermal%20and%20photodynamic%20activity%20of%20polymeric%20nanoparticles%20based%20on%20%5Cu03b1-tocopheryl%20succinate-RAFT%20block%20copolymers%20conjugated%20to%20IR-780%3C%5C%2Fa%3E.%20%3Ci%3EActa%20Biomaterialia%3C%5C%2Fi%3E%20%3Cb%3E57%3C%5C%2Fb%3E%2C%2070%5Cu201384%20%282017%29.%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27http%3A%5C%2F%5C%2Fwww.biomateriales.ictp.csic.es%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D3729048%26amp%3Bitem_key%3DVI52CUKS%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Photothermal%20and%20photodynamic%20activity%20of%20polymeric%20nanoparticles%20based%20on%20%5Cu03b1-tocopheryl%20succinate-RAFT%20block%20copolymers%20conjugated%20to%20IR-780%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raquel%22%2C%22lastName%22%3A%22Palao-Suay%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Francisco%20M.%22%2C%22lastName%22%3A%22Mart%5Cu00edn-Saavedra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mar%5Cu00eda%22%2C%22lastName%22%3A%22Rosa%20Aguilar%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Clara%22%2C%22lastName%22%3A%22Escudero-Duch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sergio%22%2C%22lastName%22%3A%22Mart%5Cu00edn-Salda%5Cu00f1a%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Francisco%20J.%22%2C%22lastName%22%3A%22Parra-Ruiz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nathan%20A.%22%2C%22lastName%22%3A%22Rohner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Susan%20N.%22%2C%22lastName%22%3A%22Thomas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nuria%22%2C%22lastName%22%3A%22Vilaboa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Julio%22%2C%22lastName%22%3A%22San%20Rom%5Cu00e1n%22%7D%5D%2C%22abstractNote%22%3A%22The%20aim%20of%20this%20work%20was%20the%20generation%20of%20a%20multifunctional%20nanopolymeric%20system%20that%20incorporates%20IR-780%20dye%2C%20a%20near-infrared%20%28NIR%29%20imaging%20probe%20that%20exhibits%20photothermal%20and%20photodynamic%20properties%3B%20and%20a%20derivate%20of%20%5Cu03b1-tocopheryl%20succinate%20%28%5Cu03b1-TOS%29%2C%20a%20mitochondria-targeted%20anticancer%20compound.%20IR-780%20was%20conjugated%20to%20the%20hydrophilic%20segment%20of%20copolymer%20PEG-b-polyMTOS%2C%20based%20on%20poly%28ethylene%20glycol%29%20%28PEG%29%20and%20a%20methacrylic%20derivative%20of%20%5Cu03b1-tocopheryl%20succinate%20%28MTOS%29%2C%20to%20generate%20IR-NP%2C%20self-assembled%20nanoparticles%20%28NPs%29%20in%20aqueous%20media%20which%20exhibit%20a%20hydrophilic%20shell%20and%20a%20hydrophobic%20core.%20During%20assembly%2C%20the%20hydrophobic%20core%20of%20IR-NP%20could%20encapsulate%20additional%20IR-780%20to%20generate%20derived%20subspecies%20carrying%20different%20amount%20of%20probe%20%28IR-NP-eIR%29.%20Evaluation%20of%20photo-inducible%20properties%20of%20IR-NP%20and%20IR-NP-eIR%20were%20thoroughly%20assessed%20in%20vitro.%20Developed%20nanotheranostic%20particles%20showed%20distinct%20fluorescence%20and%20photothermal%20behavior%20after%20excitation%20by%20a%20laser%20light%20emitting%20at%20808%20nm.%20Treatment%20of%20MDA-MB-453%20cells%20with%20IR-NP%20or%20IR-NP-eIR%20resulted%20in%20an%20efficient%20internalization%20of%20the%20IR-780%20dye%2C%20while%20subsequent%20NIR-laser%20irradiation%20led%20to%20a%20severe%20decrease%20in%20cell%20viability.%20Photocytoxicity%20conducted%20by%20IR-NP%2C%20which%20could%20not%20be%20attributed%20to%20the%20generation%20of%20lethal%20hyperthermia%2C%20responded%20to%20an%20increase%20in%20the%20levels%20of%20intracellular%20reactive%20oxygen%20species%20%28ROS%29.%20Therefore%2C%20the%20fluorescence%20imaging%20and%20inducible%20phototoxicity%20capabilities%20of%20NPs%20derived%20from%20IR-780-PEG-b-polyMTOS%20copolymer%20confer%20high%20value%20to%20these%20nanotheranostics%20tools%20in%20clinical%20cancer%20research.%5CnStatement%20of%20Significance%5CnMultifunctional%20polymeric%20nanoparticles%20%28NPs%29%20that%20combine%20imaging%20and%20therapeutic%20properties%20are%20highly%20valuable%20in%20cancer%20treatment.%20In%20this%20paper%20we%20describe%20the%20development%20of%20NPs%20that%20are%20fluorescent%20in%20the%20near-infrared%20%28NIR%29.%20This%20is%20important%20for%20their%20visualization%20in%20living%20tissues%20that%20present%20low%20absorption%20and%20low%20autofluorescence%20in%20this%20wavelength%20region%20%28between%20700%20and%201000%20nm%29.%20Moreover%2C%20NPs%20present%20photothermal%20and%20photodynamic%20properties%20when%20NIR%20irradiated%3A%20the%20NPs%20produce%20an%20efficient%20increment%20of%20temperature%20and%20increase%20the%20intracellular%20reactive%20oxygen%20species%20%28ROS%29%20when%20laser%20irradiated%20at%20808%20nm.%20These%20tuneable%20photoinduced%20properties%20make%20the%20NPs%20highly%20cytotoxic%20after%20NIR%20irradiation%20and%20provide%20a%20new%20tool%20for%20highly%20precise%20cancer%20treatment.%22%2C%22date%22%3A%22July%2015%2C%202017%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.actbio.2017.05.028%22%2C%22ISSN%22%3A%221742-7061%22%2C%22url%22%3A%22http%3A%5C%2F%5C%2Fwww.sciencedirect.com%5C%2Fscience%5C%2Farticle%5C%2Fpii%5C%2FS1742706117303100%22%2C%22collections%22%3A%5B%22HBGS28EX%22%5D%2C%22dateModified%22%3A%222017-07-05T08%3A11%3A27Z%22%7D%7D%5D%7D