Stabilized, ROS-sensitive β-cyclodextrin-grafted hyaluronic supramolecular nanocontainers for CD44-targeted anticancer drug delivery
Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility, biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive...
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| Published in: | Colloids and surfaces, B, Biointerfaces Vol. 242; p. 114081 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Netherlands
Elsevier B.V
01-10-2024
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility, biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between β-cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly(ε-caprolactone)-b-poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL-b-PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL-b-PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25 wt% (P1) and 20 wt% (P2) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1-based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1-based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.
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•Stabilized, ROS-sensitive, and active targeting HA-based micelles were prepared.•A novel silica monomer was prepared to enable in situ crosslinking.•Optimization of POEGMA density was readily achieved via a physical mixing process.•The CCL micelles are promising candidates for enhanced anticancer drug delivery. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0927-7765 1873-4367 1873-4367 |
| DOI: | 10.1016/j.colsurfb.2024.114081 |