Issue 2, 2019

Fabrication of redox-responsive doxorubicin and paclitaxel prodrug nanoparticles with microfluidics for selective cancer therapy

Abstract

Cancer is an exceptionally confounding disease that demands the development of powerful drug/drugs, without inducing heavy adverse side effects. Thus, different approaches have been applied to improve the targeted delivery of cancer drugs: for example by using nanocarriers. However, nanocarriers are foreign materials, which need further validation for their biocompatibility and biodegradability. In this study, we have chemically conjugated the hydrophilic anticancer drug doxorubicin (DOX) with the hydrophobic drug paclitaxel (PTX) through a redox-sensitive disulfide bond, abbreviated to DOX-S-S-PTX. Subsequently, due to its amphiphilic characterization, the prodrug can self-assemble into nanoparticles under microfluidic nanoprecipitation. These novel prodrug nanoparticles have a super-high drug loading degree of 89%, which is impossible to achieve by any nanocarrier systems, and can be tailored to 180 nm to deliver themselves to the target, and release DOX and PTX under redox conditions, which are often found in cancer cells. By evaluating cell viability in MDA-MB-231, MDA-MB-231/ADR and MEF cell lines, we observed that the prodrug nanoparticles effectively killed the cancer cells, and selectively conquered the MDA-MB-231/ADR. Meanwhile, MEF cells were spared due to their lack of a redox condition. The cell interaction results show that the reduced intermediate of the prodrug can also bind to parent drug biological targets. The hemolysis results show that the nanoparticles are biocompatible in blood. Computer modelling suggested that the prodrug is unlikely to bind to biological targets that parent drugs still strongly interact with. Finally, we confirm that the prodrug nanoparticles have no therapeutic effect in blood or healthy cells, but can selectively eliminate the cancer cells that meet the redox conditions to cleave the disulfide bond and release the drugs DOX and PTX.

Graphical abstract: Fabrication of redox-responsive doxorubicin and paclitaxel prodrug nanoparticles with microfluidics for selective cancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
21 Oct 2018
Accepted
28 Nov 2018
First published
03 Dec 2018

Biomater. Sci., 2019,7, 634-644

Fabrication of redox-responsive doxorubicin and paclitaxel prodrug nanoparticles with microfluidics for selective cancer therapy

X. Ma, E. Özliseli, Y. Zhang, G. Pan, D. Wang and H. Zhang, Biomater. Sci., 2019, 7, 634 DOI: 10.1039/C8BM01333K

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