Drug Delivery Nanoparticles with Locally Tunable Toxicity Made Entirely from a Light-Activatable Prodrug of Doxorubicin View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-10

AUTHORS

Carolyn Schutt, Stuart Ibsen, Eran Zahavy, Santosh Aryal, Stacey Kuo, Selin Esener, Michael Berns, Sadik Esener

ABSTRACT

PURPOSE: A major challenge facing nanoparticle-based delivery of chemotherapy agents is the natural and unavoidable accumulation of these particles in healthy tissue resulting in local toxicity and dose-limiting side effects. To address this issue, we have designed and characterized a new prodrug nanoparticle with controllable toxicity allowing a locally-delivered light trigger to convert the payload of the particle from a low to a high toxicity state. METHODS: The nanoparticles are created entirely from light-activatable prodrug molecules using a nanoprecipitation process. The prodrug is a conjugate of doxorubicin and photocleavable biotin (DOX-PCB). RESULTS: These DOX-PCB nanoparticles are 30 times less toxic to cells than doxorubicin, but can be activated to release pure therapeutic doxorubicin when exposed to 365 nm light. These nanoparticles have an average diameter of around 100 nm and achieve the maximum possible prodrug loading capacity since no support structure or coating is required to prevent loss of prodrug from the nanoparticle. CONCLUSIONS: These light activatable nanoparticles demonstrate tunable toxicity and can be used to facilitate future therapy development whereby light delivered specifically to the tumor tissue would locally convert the nanoparticles to doxorubicin while leaving nanoparticles accumulated in healthy tissue in the less toxic prodrug form. More... »

PAGES

2025-2035

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11095-017-2205-4

DOI

http://dx.doi.org/10.1007/s11095-017-2205-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091105215

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28791550


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