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Novel CD44-Targeted Albumin Nanoparticles: An Innovative Approach to Improve Breast Cancer Treatment.

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Novel nanoparticles deliver doxorubicin (DOX) effectively for breast cancer therapy. These CD44-targeted, redox-responsive nanoparticles enhance DOX

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Breast cancer remains a leading cause of mortality worldwide.
  • Doxorubicin (DOX) is a widely used chemotherapy agent with limitations like cardiotoxicity and chemoresistance.
  • Targeted drug delivery systems are needed to improve DOX efficacy and reduce side effects.

Purpose of the Study:

  • To develop novel CD44-targeted and redox-responsive nanoparticles (FNPs) for enhanced doxorubicin (DOX) delivery in breast cancer.
  • To evaluate the physicochemical properties, drug loading, and release kinetics of the developed nanoparticles.
  • To assess the in vitro efficacy of DOX-loaded FNPs (DOX@FNPs) in reducing breast cancer cell viability, metabolism, and stemness.

Main Methods:

  • Synthesis of a cationized, redox-responsive Human Serum Albumin (HSA) derivative.
  • Conjugation of HSA with cystamine and ionic complexation with hyaluronic acid (HA) to form FNPs.
  • Physicochemical characterization (size, shape, zeta potential) of FNPs.
  • Doxorubicin (DOX) loading and in vitro release studies under varying redox conditions.
  • In vitro cytotoxicity assays on 2D and 3D breast cancer models.
  • Assessment of cellular metabolism (oxygen consumption, extracellular acidification) and protein expression related to oxidative phosphorylation.
  • Evaluation of effects on breast cancer stem cells and spheroid formation.

Main Results:

  • Physicochemical characterization confirmed FNPs with a mean diameter of 240 nm and a zeta potential of 15.4 mV.
  • High DOX loading efficiency (90%) and triggered drug release (55% in 2 h) under tumor-mimicking redox conditions.
  • DOX@FNPs demonstrated enhanced cytotoxicity compared to free DOX, correlating with CD44 protein expression.
  • Significant reduction in cellular metabolism, oxygen consumption, and extracellular acidification rates.
  • Downregulation of proteins in the oxidative phosphorylation pathway, leading to reduced cell viability, motility, and stemness.

Conclusions:

  • Novel CD44-targeted, redox-responsive FNPs effectively deliver DOX for breast cancer therapy.
  • DOX@FNPs exhibit superior efficacy by enhancing cytotoxicity, reducing tumor cell metabolism, and inhibiting stem cell properties.
  • This formulation holds promise for overcoming chemoresistance and improving DOX specificity in breast cancer patients.