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Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
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Multifunctional amino acid-based nanoparticles for sequential drug delivery to overcome multidrug resistant cancer

Tengfei Wang1, Nina Sang2, Cécilia Ménard-Moyon3

  • 1CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR 3572, University of Strasbourg, ISIS, 67000 Strasbourg, France.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|April 26, 2026
PubMed

Insights

This study introduces novel nanoparticles for sequential cancer drug delivery, overcoming multidrug resistance (MDR). The nanoparticles combine chemotherapy with photothermal therapy for enhanced antitumor efficacy in MDR tumors.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Multidrug resistance (MDR) significantly limits chemotherapy effectiveness.
  • Sequential drug delivery strategies show promise over co-delivery for overcoming MDR.

Purpose of the Study:

  • To develop nanoparticles for sequential delivery of P-glycoprotein inhibitors and anticancer drugs.
  • To create a dual-action system combining chemotherapy and photothermal therapy (PTT).

Main Methods:

  • Fabrication of porous amino acid nanoparticles loaded with doxorubicin (Dox).
  • Coating nanoparticles with polydopamine (PDA) functionalized with quinidine (P-glycoprotein inhibitor) via a pH-sensitive linker.
  • Utilizing PDA's pH/glutathione sensitivity for controlled sequential drug release and PTT capabilities.

Main Results:

  • Demonstrated delayed Dox release relative to quinidine, enabling sequential delivery.
  • Controlled Dox release by adjusting PDA layer thickness.
  • Achieved significant reduction in MDR cancer cell viability (<5%) in vitro.
  • Observed substantial tumor regression in vivo through combined chemotherapy and PTT.

Conclusions:

  • The developed nanoparticles effectively overcome MDR through sequential drug delivery.
  • The combined chemotherapy and PTT approach offers high antitumor efficacy.
  • This strategy presents a promising advancement for treating MDR cancers.
Keywords:
P-glycoprotein inhibitorsPolydopamineResponsive nanomaterialsSelf-assemblyTryptophanTyrosine

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