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Preparation of Disulfide/Trisulfide Core-Cross-Linked Polycarbonate Nanocarriers for Intracellular Reduction-Triggered Drug Release.
- Source :
-
ACS macro letters [ACS Macro Lett] 2024 Nov 19; Vol. 13 (11), pp. 1433-1441. Date of Electronic Publication: 2024 Oct 09. - Publication Year :
- 2024
-
Abstract
- Polymeric nanocarriers have attracted significant attention in the field of anticancer drug delivery due to their unique advantages. However, designing nanocarriers that can maintain stability in the bloodstream while achieving specific drug release within tumor cells remains a major challenge. To address this issue, constructing reversible cross-linked polymeric nanocarriers that are sensitive to the intracellular reducible glutathione (GSH) characteristic of the tumor microenvironment is a promising strategy. Based on this, we designed and synthesized two novel six-membered bicyclic carbonate monomers containing disulfide (DSBC) and trisulfide (TSBC) bonds. Through a one-step ring-opening polymerization, a series of reduction-sensitive polycarbonate copolymers (i.e., PEG-PDSBC and PEG-PTSBC) were prepared, and doxorubicin (DOX)-loaded nanoparticles were fabricated using a nanoprecipitation method. The in vitro drug release behaviors of these nanoparticles were systematically investigated. The results showed that these polymers, due to the cross-linked structure formed by the ring-opening polymerization of their bicyclic monomers, could self-assemble into stable nanoparticles. Under different concentrations of glutathione, DOX-loaded PEG-PTSBC nanoparticles demonstrated faster drug release, indicating more optimized intracellular drug release properties. Further cytotoxicity experiments revealed that both types of blank nanoparticles exhibited good biocompatibility with the 4T1 and NIH-3T3 cells. Fluorescence microscopy and flow cytometry results further indicated that DOX-loaded PEG-PTSBC nanoparticles released more drugs in 4T1 cells, significantly inhibiting tumor cell growth compared with DOX-loaded PEG-PDSBC nanoparticles, with no noticeable difference in NIH-3T3 normal cells. In conclusion, this study suggests that trisulfide cross-linked polycarbonate-based nanocarriers hold promise as an anticancer drug delivery system that combines stability in the bloodstream with specific intracellular drug release, offering new insights for the development of novel, efficient, and safe anticancer nanomedicines.
- Subjects :
- Humans
Cell Line, Tumor
Animals
Mice
Glutathione chemistry
Glutathione metabolism
Polyethylene Glycols chemistry
Oxidation-Reduction
Cross-Linking Reagents chemistry
Doxorubicin pharmacology
Doxorubicin chemistry
Doxorubicin administration & dosage
Disulfides chemistry
Polycarboxylate Cement chemistry
Nanoparticles chemistry
Drug Liberation
Drug Carriers chemistry
Sulfides chemistry
Sulfides pharmacology
Sulfides chemical synthesis
Sulfides pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 2161-1653
- Volume :
- 13
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- ACS macro letters
- Publication Type :
- Academic Journal
- Accession number :
- 39383241
- Full Text :
- https://doi.org/10.1021/acsmacrolett.4c00443