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Dextran-Curcumin Nanosystems Inhibit Cell Growth and Migration Regulating the Epithelial to Mesenchymal Transition in
Emilia Bevacqua1, Manuela Curcio1, Federica Saletta2,3
1Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.
Abstract:
Functional nanocarriers which are able to simultaneously vectorize drugs to the site of interest and exert their own cytotoxic activity represent a significant breakthrough in the search for effective anticancer strategies with fewer side effects than conventional chemotherapeutics. Here, we propose previously developed, self-assembling dextran-curcumin nanoparticles for the treatment of prostate cancer in combination therapy with Doxorubicin (DOXO). Biological effectiveness was investigated by evaluating the cell viability in either cancer and normal cells, reactive oxygen species (ROS) production, apoptotic effect, interference with the cell cycle, and the ability to inhibit cell migration and reverse the epithelial to mesenchymal transition (EMT). The results proved a significant enhancement of curcumin efficiency upon immobilization in nanoparticles: IC50 reduced by a half, induction of apoptotic effect, and improved ROS production (from 67 to 134%) at low concentrations. Nanoparticles guaranteed a pH-dependent DOXO release, with a more efficient release in acidic environments. Finally, a synergistic effect between nanoparticles and Doxorubicin was demonstrated, with the free curcumin showing additive activity. Although in vivo studies are required to support the findings of this study, these preliminary in vitro data can be considered a proof of principle for the design of an effective therapy for prostate cancer treatment.
Insights
Self-assembling dextran-curcumin nanoparticles show enhanced efficacy for prostate cancer treatment. Combined with Doxorubicin, these nanoparticles demonstrate synergistic effects and reduced toxicity, offering a promising new therapeutic strategy.
Area of Science:
- Nanomedicine
- Cancer Therapy
- Drug Delivery Systems
Background:
- Conventional chemotherapy presents limitations in efficacy and side effects.
- Developing targeted drug delivery systems is crucial for improved cancer treatment.
- Functional nanocarriers offer dual action: drug delivery and intrinsic cytotoxicity.
Purpose of the Study:
- To evaluate dextran-curcumin nanoparticles in combination therapy for prostate cancer.
- To assess the biological effectiveness of these nanoparticles in vitro.
- To investigate synergistic effects with Doxorubicin (DOXO).
Main Methods:
- Synthesis of self-assembling dextran-curcumin nanoparticles.
- In vitro evaluation of cell viability in cancer and normal cells.
- Assessment of reactive oxygen species (ROS) production, apoptosis, cell cycle, migration, and epithelial to mesenchymal transition (EMT).
- pH-dependent drug release studies for DOXO.
Main Results:
- Immobilization of curcumin in nanoparticles significantly enhanced its efficacy (halved IC50).
- Nanoparticles increased ROS production (67% to 134%) and induced apoptosis at low concentrations.
- pH-dependent DOXO release was observed, with higher release in acidic environments.
- A synergistic effect was demonstrated between nanoparticles and DOXO, with additive activity from free curcumin.
Conclusions:
- Dextran-curcumin nanoparticles represent a promising strategy for prostate cancer treatment.
- The combination therapy shows enhanced efficacy and potential for reduced side effects.
- Further in vivo studies are warranted to validate these in vitro findings.
