Disulfide-Functionalized Covalent Organic Frameworks as Nanocarriers Realizing Programmed Cellular Internalization...

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Covalent organic frameworks (COFs) show promise for drug delivery but face challenges with cell penetration and controlled release.
• Developing stimuli-responsive nanocarriers is crucial for targeted and effective pharmaceutical applications.

Purpose of the Study:

• To engineer glutathione-sensitive COFs (SSx-COFs) with tunable disulfide densities for enhanced bioactive molecule delivery.
• To investigate the impact of disulfide incorporation on cellular uptake, drug release kinetics, and in vivo antitumor efficacy.

Main Methods:

• Synthesis of SSx-COFs with varying disulfide densities by integrating disulfide motifs into COF backbones.
• Characterization of COF nanocarriers for surface area, drug loading capacity, and disulfide content.
• Evaluation of cellular uptake mechanisms via thiol-disulfide exchange and assessment of in vitro/in vivo drug release and antitumor activity.

Main Results:

• SSx-COFs exhibited high surface areas and drug loading capacities.
• Disulfide incorporation significantly enhanced COF cellular uptake and accelerated drug release, controllable by disulfide density.
• Thiol-disulfide exchange mediated the enhanced cellular internalization pathway.
• SS70-COF loaded with doxorubicin demonstrated potent in vitro and in vivo antitumor efficacy.

Conclusions:

• Surface disulfide engineering is a viable strategy to enhance the intracellular delivery efficiency of nanocarriers.
• Glutathione-sensitive SSx-COFs offer a promising platform for stimuli-responsive drug delivery systems.
• This approach provides valuable insights for designing next-generation nanomedicines for cancer therapy.