Home
Resources
Publications
Reactive Oxygen Species-Responsive Nanoprodrug With Quinone Methides-Mediated GSH Depletion for Improved Chlorambucil Breast Cancers Therapy

Reactive Oxygen Species-Responsive Nanoprodrug With Quinone Methides-Mediated GSH Depletion for Improved Chlorambucil Breast Cancers Therapy

Cheng-Qiong Luo, Yu-Xin Zhou, Tian-Jiao Zhou, Lei Xing, Peng-Fei Cui, Minjie Sun, Liang Jin, Na Lu, Hu-Lin Jiang

J Control Release. 2018 Mar 28;274:56-68.

PMID: 29409835

Abstract:

Prodrug-based stimuli-responsive vectors have emerged as highly promising platform. Inspired by the fact that antioxidant systems including glutathione (GSH) make cancer cells adapt to oxidative stress and play a role in the inactivation of alkylating agents like chlorambucil (CHL) inside tumor cells, while arylboronic acid could transform into GSH depleting agent quinone methide (QM) upon degradation by reactive oxygen species (ROS) over-expressed in tumor cells, a ROS-responsive nanoprodrug (denoted by PPAHC) of CHL was established by integrating CHL into diols-containing hydrophilic polymer with self-immolative linker 4-(hydroxymethyl)phenylboronic acid (HPBA). The prodrug could form core-shell nanoparticle and possess high stability during storage. Drug release profile of PPAHC nanoprodrug demonstrated that nature CHL could be quickly released from PPAHC nanoprodrug in the presence of hydrogen peroxide (H2O2). Moreover, PPAHC nanoprodrug showed improved therapeutic efficiency compared to CHL via anti-proliferative study and cell apoptosis assay. Further measurement of GSH content and ROS levels in tumor cells suggested that the synergistic impact resulted from QM-mediated GSH reduction and CHL-induced further oxidative stress insults to tumor cells. In vivo tumor suppression effect and biocompatibility indicated the superiorities of PPAHC nanoprodrug. Accordingly, PPAHC provides a new approach as a ROS-responsive CHL delivery system and has a great potential for cancer therapy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS793937	2-(Hydroxymethyl)phenylboronic acid			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: