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dc.contributor.authorYildiz, Tugba
dc.contributor.authorGu, Renpeng
dc.contributor.authorZauscher, Stefan
dc.contributor.authorBetancourt, Tania
dc.date.accessioned2019-08-05T17:31:49Z
dc.date.available2019-08-05T17:31:49Z
dc.date.issued2018-10-31
dc.identifier.citationYildiz, T., Gu, R., Zauscher, S., & Betancourt, T. (2018). Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer. International Journal of Nanomedicine, 2018:13, pp. 6961-6986.en_US
dc.identifier.issn1178-2013
dc.identifier.urihttps://digital.library.txstate.edu/handle/10877/8454
dc.description.abstractIntroduction: 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.en_US
dc.formatText
dc.format.extent26 pages
dc.format.medium1 file (.pdf)
dc.language.isoen_USen_US
dc.publisherDove Medical Pressen_US
dc.sourceInternational Journal of Nanomedicine, 2018, Vol. 13, pp. 6961-6986
dc.subjectPEGen_US
dc.subjectPLA
dc.subjectPLGA
dc.subjectBlock copolymers
dc.subjectDrug delivery
dc.subjectEnzymatic activation
dc.subjectFluorescence imaging
dc.subjectNanomedicine
dc.subjectNanoparticles
dc.subjectNanoprecipitation
dc.subjectPoly-l-lysine
dc.subjectTheranostics
dc.titleDoxorubicin-loaded Protease-activated Near-infrared Fluorescent Polymeric Nanoparticles for Imaging and Therapy of Canceren_US
txstate.documenttypeArticle
dc.identifier.doihttps://doi.org/10.2147/IJN.S174068
dc.rights.licenseThis work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms/php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. \
txstate.departmentChemistry and Biochemistry


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