Self-folded redox/acid dual-responsive nanocarriers for anticancer drug delivery

Abstract

Self-folded redox/acid dual-responsive nanocarriers (RAD-NCs) are developed for physiologically triggered delivery of anticancer drugs. The evidenced redox/acid responsiveness, facile decoration of ligands, and active tumor-targeting capability of RAD-NCs suggest their potential as a promising formulation for tumor-targeted chemotherapy.

Figure 1

Schematic design of the redox/acid dual-responsive nanocarriers (RAD-NCs) for anticancer drug delivery. A) Schematic illustration of the formation and structural transitions of RAD-NCs for targeted intracellular drug delivery. i) Self-assemble the graft copolymer with DOX into nanocarriers; ii) decoration of the targeting ligand (folic acid) with thiol groups generated by partial cleavage of disulfide using glutathione; iii) intracellular delivery of RAD-NCs. B) Schematic of the chemical structure of the graft copolymer and DOX. The scissors represent cleavage sites.

Figure 2

Characterization of graft; copolymer and nanocarriers. A) Respenstative TEM image of RAD-NCs.. Scale bar: 200 nm. B) Hydrodynamic size of RAD-NCs measured by DLS. Iinset: TEM image of RAD-NCs (zoom in). Scale bar: 100 nm.

Figure 3

A) Respenstative TEM images of nanocarriers treated with GSH (10 mM) and acid (pH 5.0): GSH (left), aciid (middle) and GSH/acid (right). Scale bars: 200 nm. B) DOX release profiles of DOX-loaded micelles in different buffers at 37 °C. Data represent mean ± SD (n=3).

Figure 4

The cellular uptake behavior and cytotoxicity of DOX/RAD-NCs and DOX/FA-RAD-NCs toward HeLa cell line. (A, B) Intracellular trafficking of DOX/RAD-NCs (A) and DOX/FA-RAD-NCs (b) on HeLa cell line observed by CLSM. The late endosomes and lysosomes were stained by LysoTracker Green, and the nuclei were stained by Hoechst 33342. Scale bar: 10 μm. (C, D) Viabilities of HeLa cells incubated with blank medium, free DOX, DOX/RAD-NCs and DOX/FA-RAD-NCs at various DOX concentrations for C) 24 h and D) 48 h. The horizontal ordinate indicates the concentration of DOX. Error bars indicate s.d. (n=4).