Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer

Tugba Yildiz,1 Renpeng Gu,2 Stefan Zauscher,2 Tania Betancourt1,3 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, 2Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 3Department of Chemistry and Biochemist...

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Autores principales:	Yildiz T, Gu R, Zauscher S, Betancourt T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Nanomedicine theranostics drug delivery fluorescence imaging enzymatic activation nanoprecipitation block copolymers PLGA PLA PEG poly-L-lysine nanoparticles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/46f8f7ab66434ca5b7cd3022e5862bad
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spelling	oai:doaj.org-article:46f8f7ab66434ca5b7cd3022e5862bad2021-12-02T06:57:12ZDoxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer1178-2013https://doaj.org/article/46f8f7ab66434ca5b7cd3022e5862bad2018-10-01T00:00:00Zhttps://www.dovepress.com/doxorubicin-loaded-protease-activated-near-infrared-fluorescent-polyme-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tugba Yildiz,1 Renpeng Gu,2 Stefan Zauscher,2 Tania Betancourt1,3 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, 2Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 3Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA Introduction: Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. Material and methods: In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core–shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-L-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-L-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules. Results: The spherical nanoparticles had an average size of 60–80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-L-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2–2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers. Conclusion: Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells. Keywords: nanomedicine, theranostics, drug delivery, fluorescence imaging, enzymatic activation, nanoprecipitation, block copolymers, PLGA, PLA, PEG, poly-L-lysine, nanoparticlesYildiz TGu RZauscher SBetancourt TDove Medical PressarticleNanomedicinetheranosticsdrug deliveryfluorescence imagingenzymatic activationnanoprecipitationblock copolymersPLGAPLAPEGpoly-L-lysinenanoparticlesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 6961-6986 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nanomedicine theranostics drug delivery fluorescence imaging enzymatic activation nanoprecipitation block copolymers PLGA PLA PEG poly-L-lysine nanoparticles Medicine (General) R5-920
spellingShingle	Nanomedicine theranostics drug delivery fluorescence imaging enzymatic activation nanoprecipitation block copolymers PLGA PLA PEG poly-L-lysine nanoparticles Medicine (General) R5-920 Yildiz T Gu R Zauscher S Betancourt T Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer
description	Tugba Yildiz,1 Renpeng Gu,2 Stefan Zauscher,2 Tania Betancourt1,3 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, 2Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 3Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA Introduction: Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. Material and methods: In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core–shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-L-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-L-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules. Results: The spherical nanoparticles had an average size of 60–80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-L-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2–2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers. Conclusion: Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells. Keywords: nanomedicine, theranostics, drug delivery, fluorescence imaging, enzymatic activation, nanoprecipitation, block copolymers, PLGA, PLA, PEG, poly-L-lysine, nanoparticles
format	article
author	Yildiz T Gu R Zauscher S Betancourt T
author_facet	Yildiz T Gu R Zauscher S Betancourt T
author_sort	Yildiz T
title	Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer
title_short	Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer
title_full	Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer
title_fullStr	Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer
title_full_unstemmed	Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer
title_sort	doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/46f8f7ab66434ca5b7cd3022e5862bad
work_keys_str_mv	AT yildizt doxorubicinloadedproteaseactivatednearinfraredfluorescentpolymericnanoparticlesforimagingandtherapyofcancer AT gur doxorubicinloadedproteaseactivatednearinfraredfluorescentpolymericnanoparticlesforimagingandtherapyofcancer AT zauschers doxorubicinloadedproteaseactivatednearinfraredfluorescentpolymericnanoparticlesforimagingandtherapyofcancer AT betancourtt doxorubicinloadedproteaseactivatednearinfraredfluorescentpolymericnanoparticlesforimagingandtherapyofcancer
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Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer

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