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

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.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Schutt C,Ibsen S,Zahavy E,Aryal S,Kuo S,Esener S,Berns M,Esener S

doi

10.1007/s11095-017-2205-4

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

2025-2035

issue

10

eissn

0724-8741

issn

1573-904X

pii

10.1007/s11095-017-2205-4

journal_volume

34

pub_type

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