Purpose <p>Effective drug delivery remains a significant challenge in breast cancer therapy. This study was designed to develop&#xa0;a salep polysaccharide-based multi-responsive nanogel (NG) for the controlled delivery of doxorubicin (DOX) to&#xa0;breast cancer cells, with the goal of enhancing targeted treatment and reducing systemic toxicity.</p> Methods <p>The NG was synthesized using radical precipitation/dispersion polymerization, incorporating magnetic graphene&#xa0;oxide (MGO), N-isopropylacrylamide (NIPAM), 2-dimethylaminoethyl acrylate (DMAEA), and a redox-responsive&#xa0;crosslinker, N,N’-Bis(acryloyl)cystamine (BAC). Structural characterization by DLS and TEM confirmed a semi-spherical&#xa0;morphology, with a mean hydrodynamic diameter of approximately 78 nm and a polydispersity index (PDI)&#xa0;of 0.335. FT-IR, EDAX, and XRD validated the successful incorporation of components while SEM and AFM provided&#xa0;detailed insights into the surface morphology.</p> Results <p>The NG demonstrated a high DOX loading capacity (92%) and an efficient drug release profile. Under acidic (pH 5)&#xa0;and reductive (10 mM glutathione) conditions, 96% of DOX was released, decreasing the drug release time from 10&#xa0;hours to approximately 60 minutes. The release kinetics were consistent with the Korsmeyer-Peppas model,&#xa0;indicative of Fickian diffusion. Furthermore, cytotoxicity evaluations using the MTT assay revealed low toxicity in&#xa0;normal MCF-10A cells, supporting the potential of the NG to improve therapeutic efficacy while minimizing adverse&#xa0;effects.</p> Conclusion <p>The salep polysaccharide-based multi-responsive NG represents a promising targeted drug delivery system for&#xa0;breast cancer therapy. Its high DOX loading capacity, rapid and controlled drug release under tumor-like conditions,&#xa0;and minimal toxicity underscore its potential to advance the application of biopolymer-based nanogels in precision&#xa0;oncology.</p> Graphical Abstract <p></p>

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Salep Polysaccharide-Based Multi-Responsive Nanogel for Controlled Doxorubicin Release: Structural Characterization and Functional Evaluation for Targeted Breast Cancer Therapy

  • Ghasem Rezanejade Bardajee,
  • Hossein Mahmoodian,
  • Negin Shafiei,
  • Mahnaz Rouhi,
  • Golnaz Sang,
  • Mohammad Amin Karimi

摘要

Purpose

Effective drug delivery remains a significant challenge in breast cancer therapy. This study was designed to develop a salep polysaccharide-based multi-responsive nanogel (NG) for the controlled delivery of doxorubicin (DOX) to breast cancer cells, with the goal of enhancing targeted treatment and reducing systemic toxicity.

Methods

The NG was synthesized using radical precipitation/dispersion polymerization, incorporating magnetic graphene oxide (MGO), N-isopropylacrylamide (NIPAM), 2-dimethylaminoethyl acrylate (DMAEA), and a redox-responsive crosslinker, N,N’-Bis(acryloyl)cystamine (BAC). Structural characterization by DLS and TEM confirmed a semi-spherical morphology, with a mean hydrodynamic diameter of approximately 78 nm and a polydispersity index (PDI) of 0.335. FT-IR, EDAX, and XRD validated the successful incorporation of components while SEM and AFM provided detailed insights into the surface morphology.

Results

The NG demonstrated a high DOX loading capacity (92%) and an efficient drug release profile. Under acidic (pH 5) and reductive (10 mM glutathione) conditions, 96% of DOX was released, decreasing the drug release time from 10 hours to approximately 60 minutes. The release kinetics were consistent with the Korsmeyer-Peppas model, indicative of Fickian diffusion. Furthermore, cytotoxicity evaluations using the MTT assay revealed low toxicity in normal MCF-10A cells, supporting the potential of the NG to improve therapeutic efficacy while minimizing adverse effects.

Conclusion

The salep polysaccharide-based multi-responsive NG represents a promising targeted drug delivery system for breast cancer therapy. Its high DOX loading capacity, rapid and controlled drug release under tumor-like conditions, and minimal toxicity underscore its potential to advance the application of biopolymer-based nanogels in precision oncology.

Graphical Abstract