# Redox-Responsive Self-Assembled Amphiphilic Nanosheets from Polyglycerol Sulfate–Lipoic Acid Copolymers for Targeted Cancer Drug Delivery

## TL;DR

This study introduces a redox-responsive drug delivery system that releases anticancer drugs specifically in cancer cell environments.

## Contribution

A novel amphiphilic nanosheet system using polyglycerol sulfate and lipoic acid for targeted drug release in cancer cells.

## Key findings

- The nanosheets degrade and release cargo in response to elevated glutathione levels in cancer cells.
- The system successfully loaded and released paclitaxel, an anticancer drug, in vitro.
- Morphological changes were confirmed using SEM, Cryo-TEM, and Cryo-ET.

## Abstract

Targeted drug delivery systems that are stimuli-responsive
offer
great potential for enhancing the therapeutic activity of drugs, decreasing
off-target effects, and improving bioavailability. This proof-of-concept
study introduces an amphiphilic drug delivery system (DDS) capable
of loading hydrophobic cargo. Elevated glutathione (GSH) levels, characteristic
of certain types of cancer cells’ microenvironment, degrade
the nanostructures and release the cargo. Linear polyglycerol sulfate
(LPGS), known for its excellent biocompatibility, is combined with
lipoic acid (LA). LA facilitates the formation of cross-linked nanosheet
amphiphiles sensitive to reductive conditions. Morphological changes
are observed by scanning electron microscopy (SEM), cryogenic transmission
electron microscopy (Cryo-TEM), and cryogenic electron tomography
(Cryo-ET) upon UV irradiation (hν), creating
a stable aggregate for loading hydrophobic cargo and assembling into
sheets at elevated concentrations. The resulting material displays
controlled release of model dyes under increased levels of GSH, tunable
by the polymer size and LPGS:LA acid ratios. This behavior enhances
targeted therapy and reduced off-target effects. Further loading with
paclitaxel and subsequent release, together with in vitro assays, demonstrates the system’s compatibility with an anticancer
drug.