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Purpose <p>Quercetin exhibits anticancer activity but its therapeutic potential is limited by poor solubility, low bioavailability, and limited tumor selectivity. This study reports the development of quercetin-encapsulated galactosylated chitosan–decorated albumin nanoparticles (Q-Alb-GC NPs) designed to integrate size-mediated tumor accumulation with transporter-associated cellular uptake.</p> Methods <p>Galactosylated chitosan was synthesized <i>via</i> a Maillard reaction and used to functionalize the albumin NPs prepared by desolvation technique.</p> Results <p>The optimized formulation exhibited a mean particle size of 189.1 ± 2.5&#xa0;nm, positive zeta potential (25.34 ± 1.00 mV), narrow size distribution (PDI 0.221 ± 0.008), and high quercetin encapsulation efficiency (85.9 ± 0.023%). Sustained drug release was observed compared with free quercetin. In vitro studies demonstrated enhanced cytotoxicity of Q-Alb-GC NPs in A549 lung cancer cells, with a reduced IC₅₀ relative to the free drug, while maintaining lower toxicity toward RAW 264.7 macrophages. Surface functionalization with galactosylated chitosan significantly increased cellular uptake, confirming effective GLUT-1–mediated internalization. Molecular docking supported favorable galactose binding within the GLUT-1 pocket.</p> Conclusion <p>Overall, these findings demonstrate that Q-Alb-GC NPs represent a metabolic-responsive potential drug delivery platform that combines passive tumor accumulation with GLUT-1–targeted cellular uptake, resulting in enhanced anticancer efficacy. This approach offers a promising approach to improve tumor selectivity and reduce off-target effects in cancer therapy.</p>

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Galactosylated Chitosan-Albumin Hybrid Nanoparticles for Ligand-Enhanced Quercetin Delivery in Lung Cancer

  • 期刊论文

  • 发表日期：

    2026年6月20日

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  • Aida Nur Fadhilah,
  • Ebrahim Sadaqa,
  • Fransiska Christydira Sekaringtyas,
  • A’liyatur Rosyidah,
  • Gita Syahputra,
  • Nuralih,
  • Elpri Eka Permadi,
  • Etik Mardliyati,
  • Arien Dwitrie,
  • Prasetya Widodo,
  • Rony Martien,
  • Sjaikhurrizal El Muttaqien

摘要

Purpose

Quercetin exhibits anticancer activity but its therapeutic potential is limited by poor solubility, low bioavailability, and limited tumor selectivity. This study reports the development of quercetin-encapsulated galactosylated chitosan–decorated albumin nanoparticles (Q-Alb-GC NPs) designed to integrate size-mediated tumor accumulation with transporter-associated cellular uptake.

Methods

Galactosylated chitosan was synthesized via a Maillard reaction and used to functionalize the albumin NPs prepared by desolvation technique.

Results

The optimized formulation exhibited a mean particle size of 189.1 ± 2.5 nm, positive zeta potential (25.34 ± 1.00 mV), narrow size distribution (PDI 0.221 ± 0.008), and high quercetin encapsulation efficiency (85.9 ± 0.023%). Sustained drug release was observed compared with free quercetin. In vitro studies demonstrated enhanced cytotoxicity of Q-Alb-GC NPs in A549 lung cancer cells, with a reduced IC₅₀ relative to the free drug, while maintaining lower toxicity toward RAW 264.7 macrophages. Surface functionalization with galactosylated chitosan significantly increased cellular uptake, confirming effective GLUT-1–mediated internalization. Molecular docking supported favorable galactose binding within the GLUT-1 pocket.

Conclusion

Overall, these findings demonstrate that Q-Alb-GC NPs represent a metabolic-responsive potential drug delivery platform that combines passive tumor accumulation with GLUT-1–targeted cellular uptake, resulting in enhanced anticancer efficacy. This approach offers a promising approach to improve tumor selectivity and reduce off-target effects in cancer therapy.