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<p>Nanoparticle-based targeted therapy offers precise drug delivery with enhanced efficacy and reduced off-target effects for prostate cancer treatment. This study developed hyaluronic acid (HA)-coated shikonin-loaded PLGA nanoparticles (HA-PEG-PLGA-shikonin NPs) to target CD44 + LNCAP prostate cancer cells. The NPs were synthesized using single emulsion solvent evaporation, followed by HA conjugation via EDC/NHS chemistry. The resulting NPs had a particle size of 142 ± 24 nm, zeta potential of -17 ± 2.3 mV, and 92 ± 6.1% encapsulation efficiency. Enhanced uptake was observed in CD44 + LNCAP cells for HA-coated NPs. Cytotoxicity studies showed reduced IC50 values of 70.02 µg/mL (24 h) and 48.78 µg/mL (48 h), compared to 111.54 µg/mL and 54.02 µg/mL for uncoated NPs. Apoptosis analysis revealed 68.37% late apoptosis with HA-coated NPs versus 45.87% with uncoated ones. Spheroid assays showed 17.69% tumor size reduction after 96 h, compared to 15.75% and 9.8% for uncoated NPs and plain shikonin, respectively. Migration rates dropped to 10.24% with HA-coated NPs, versus 14.39% (uncoated) and 14.76% (control). CAM assays demonstrated 83.87% greater angiogenesis inhibition than uncoated NPs. These findings highlight HA-PEG-PLGA-shikonin NPs as a promising strategy for enhanced targeted prostate cancer therapy.</p>

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Hyaluronic Acid-Functionalized PEG-PLGA Nanoparticles for Targeted Shikonin Delivery: A Potential Therapeutic Approach for Prostate Cancer

  • 期刊论文

  • 发表日期：

    2025年10月15日

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  • Aria Mohabbat,
  • Hamed Dadashi,
  • Milad Mashinchian,
  • Alireza Karimian-Shaddel,
  • Khosro Adibkia,
  • Hossein Nazemiyeh,
  • Somayeh Vandghanooni,
  • Morteza Eskandani

摘要

Nanoparticle-based targeted therapy offers precise drug delivery with enhanced efficacy and reduced off-target effects for prostate cancer treatment. This study developed hyaluronic acid (HA)-coated shikonin-loaded PLGA nanoparticles (HA-PEG-PLGA-shikonin NPs) to target CD44 + LNCAP prostate cancer cells. The NPs were synthesized using single emulsion solvent evaporation, followed by HA conjugation via EDC/NHS chemistry. The resulting NPs had a particle size of 142 ± 24 nm, zeta potential of -17 ± 2.3 mV, and 92 ± 6.1% encapsulation efficiency. Enhanced uptake was observed in CD44 + LNCAP cells for HA-coated NPs. Cytotoxicity studies showed reduced IC50 values of 70.02 µg/mL (24 h) and 48.78 µg/mL (48 h), compared to 111.54 µg/mL and 54.02 µg/mL for uncoated NPs. Apoptosis analysis revealed 68.37% late apoptosis with HA-coated NPs versus 45.87% with uncoated ones. Spheroid assays showed 17.69% tumor size reduction after 96 h, compared to 15.75% and 9.8% for uncoated NPs and plain shikonin, respectively. Migration rates dropped to 10.24% with HA-coated NPs, versus 14.39% (uncoated) and 14.76% (control). CAM assays demonstrated 83.87% greater angiogenesis inhibition than uncoated NPs. These findings highlight HA-PEG-PLGA-shikonin NPs as a promising strategy for enhanced targeted prostate cancer therapy.