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Updated: Jun 30, 2026

Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
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.
Abstract:
Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.
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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