Stabilized, ROS-sensitive β-cyclodextrin-grafted hyaluronic supramolecular nanocontainers for CD44-targeted...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems
• Oncology

Background:

• Hyaluronic acid (HA)-based nanocontainers offer biocompatibility and CD44 targeting for cancer therapy.
• Existing HA-based nanomedicines face challenges in multi-step synthesis, leading to variability and scale-up issues.
• Need for facile and robust strategies for advanced HA-based nanomedicine development.

Purpose of the Study:

• To develop a simplified, additive-free method for creating stable, responsive HA-based nanomedicines.
• To integrate in situ crosslinking and supramolecular complexation for enhanced drug delivery.
• To evaluate the efficacy of the developed nanomedicines in targeting and killing cancer cells.

Main Methods:

• Preparation of a silica monomer with a cross-linkable diethoxysilyl unit for in situ crosslinking.
• Fabrication of reactive oxygen species (ROS)-sensitive supramolecular polymer constructs via host-guest complexation.
• Formation of core-crosslinked (CCL) micelles using HA-grafted HA (HA-CD) and ferrocene-functionalized polymers.

Main Results:

• Successfully fabricated Fc-POEGMA/Fc-PCL-b-PDESPMA@HA-CD nanomedicines with integrated stealth, targeting, and crosslinking features.
• P1-based CCL micelles exhibited excellent colloidal stability and intracellular aggregation upon exposure to ROS, promoting cargo release.
• P1-based nanomedicines showed enhanced cytotoxicity in CD44-positive HeLa cells compared to CD44-negative MCF-7 cells.

Conclusions:

• Developed a facile strategy for HA-based nanomedicines using in situ crosslinking and supramolecular complexation.
• The nanomedicines possess superior extracellular stability and efficient intracellular destabilization for improved drug delivery.
• This approach offers a promising platform for enhanced anticancer therapy with reduced batch-to-batch variations.