Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro

Ayman Khdair1, Hitesh Handa, Guangzhao Mao

  • 1Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA.

Insights

This study shows that combining doxorubicin chemotherapy with photodynamic therapy (PDT) using methylene blue, delivered via nanoparticles, effectively overcomes drug resistance in cancer cells. This approach enhances drug delivery and boosts cancer cell death.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Research

Background:

  • Drug resistance, particularly due to efflux transporters like P-glycoprotein (P-gp), significantly limits anticancer drug efficacy.
  • Photodynamic therapy (PDT) using methylene blue, a known P-gp inhibitor, presents a potential strategy to reverse this resistance.

Purpose of the Study:

  • To evaluate the efficacy of nanoparticle-mediated combination therapy of doxorubicin and methylene blue-based PDT in overcoming drug resistance in cancer cells.
  • To investigate the role of simultaneous drug delivery via nanoparticles in enhancing intracellular drug accumulation and subsequent cytotoxicity.

Main Methods:

  • Aerosol OT (AOT)-alginate nanoparticles were formulated for co-delivery of doxorubicin and methylene blue.
  • Drug-resistant NCI/ADR-RES cells were treated with nanoparticle-encapsulated drugs and photoactivated PDT (665 nm).
  • Cytotoxicity, apoptosis, necrosis, intracellular drug accumulation, and reactive oxygen species (ROS) production were assessed using flow cytometry, fluorescence microscopy, and HPLC.

Main Results:

  • Nanoparticle encapsulation significantly enhanced the cytotoxicity of the combined doxorubicin and methylene blue therapy in resistant cells.
  • The combination therapy led to a significant induction of apoptosis and necrosis, correlated with improved intracellular and nuclear drug delivery.
  • Nanoparticle-mediated combination therapy resulted in substantially elevated ROS production compared to single-drug treatments.

Conclusions:

  • Nanoparticle-mediated delivery of doxorubicin and methylene blue, combined with PDT, effectively overcomes cancer drug resistance mechanisms.
  • This combination strategy significantly improves anticancer efficacy by enhancing drug accumulation and inducing cell death pathways.
  • The findings highlight the potential of combining nanotechnology with PDT for treating drug-resistant cancers.

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