Issue 28, 2017

Single-trigger dual-responsive nanoparticles for controllable and sequential prodrug activation

Abstract

Here we have developed a novel approach where two synergistically acting drugs were completely inactivated upon chemical immobilization on a nanoparticle template and activated in response to a chemical stimulus. The activation rate of each drug payload is controlled using a biologically inert bioorthogonal chemistry approach. By exploiting the subtle differences in the ‘click-to-release’ bioorthogonal reaction, we engineered a single delivery platform capable of releasing the payloads in a time-staggered manner in response to a single dose of a highly specific, yet reactive, small molecule. Incorporation of both di-axial, ‘fast release’, and di-equatorial, ‘slow release’, TCO linkers into our nanodrug assembly inhibited the activity of the drug molecules and enabled us to control the timing and activation of each payload. This single-trigger dual-responsive nanoparticle construct and its release kinetics were characterized using two molecular fluorescent probes and tested in vitro for efficient delivery of molecular payloads. In this manuscript we show that this approach was also successful in the treatment of triple negative BT-20 breast cancer cells. Our nanodrug loaded with the slow-releasing doxorubicin and fast-releasing PAC-1 prodrugs displayed a greater therapeutic response than the nanodrug which released both payloads simultaneously.

Graphical abstract: Single-trigger dual-responsive nanoparticles for controllable and sequential prodrug activation

Supplementary files

Article information

Article type
Paper
Submitted
10 Jun 2017
Accepted
24 Jun 2017
First published
30 Jun 2017

Nanoscale, 2017,9, 10020-10030

Single-trigger dual-responsive nanoparticles for controllable and sequential prodrug activation

N. M. Robertson, Y. Yang, I. Khan, V. E. LaMantia, M. Royzen and M. V. Yigit, Nanoscale, 2017, 9, 10020 DOI: 10.1039/C7NR04138A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements