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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalPharmaceutical Research
DOIs
StateAccepted/In press - Aug 8 2017
Externally publishedYes

Fingerprint

Prodrugs
Drug delivery
Nanoparticles
Doxorubicin
Toxicity
Light
Pharmaceutical Preparations
Poisons
Tissue
Biotin
Chemotherapy
Tumors
Drug Therapy
Coatings
Molecules
Therapeutics

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Drug Delivery Nanoparticles with Locally Tunable Toxicity Made Entirely from a Light-Activatable Prodrug of Doxorubicin. / Schutt, Carolyn; Ibsen, Stuart; Zahavy, Eran; Aryal, Santosh; Kuo, Stacey; Esener, Selin; Berns, Michael; Esener, Sadik.

In: Pharmaceutical Research, 08.08.2017, p. 1-11.

Research output: Contribution to journalArticle

Schutt, Carolyn ; Ibsen, Stuart ; Zahavy, Eran ; Aryal, Santosh ; Kuo, Stacey ; Esener, Selin ; Berns, Michael ; Esener, Sadik. / Drug Delivery Nanoparticles with Locally Tunable Toxicity Made Entirely from a Light-Activatable Prodrug of Doxorubicin. In: Pharmaceutical Research. 2017 ; pp. 1-11.
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