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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Circumventing Drug Resistance Pathways with a Nanoparticle-Based Photodynamic Method
Yan Liu1,2, Qelger Bao3, Zheng Chen4
1State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
Abstract:
Drug resistance remains the dominant impediment for cancer therapy, not only because compensatory drug resistance pathways are always activated, but also because of the cross-resistance of cancer cells to unrelated therapeutics. Herein, chemodrug-sensitive cancer cells, intrinsic drug-resistant cells, and acquired resistant cells were employed to uncover their biological response to a nanoparticle-based photodynamic method in tumoral, cellular, and molecular levels. We observed that nanoparticle-based photodynamic process with high therapeutic efficiency, intracellular delivery, and tumor penetration effect resulted in the indiscriminate and significant therapeutic outcome, in contrast to the diversiform effect of first-line chemo-drug, Temozolomide (TMZ). By real-time quantitative PCR array technique, we revealed that signals in classical resistance pathways were unaffected or downregulated, and photodynamic effect initiates cell apoptosis via downstream genes. The discovery that nanoparticulate photodynamic therapy bypasses the signals in multiple resistant pathways may imply an alternative route for combating drug resistance of cancer.
Insights
Nanoparticle photodynamic therapy overcomes cancer drug resistance by bypassing known resistance pathways. This approach shows significant therapeutic outcomes across sensitive and resistant cancer cells, offering a new strategy against treatment failure.
Area of Science:
- Biomedical Engineering
- Cancer Therapy
- Nanomedicine
Background:
- Drug resistance is a major challenge in cancer treatment, involving compensatory pathways and cross-resistance.
- Existing therapies like Temozolomide (TMZ) can have limited or varied effects on resistant cancer cells.
Purpose of the Study:
- To investigate the efficacy of a nanoparticle-based photodynamic therapy (nano-PDT) against drug-sensitive and drug-resistant cancer cells.
- To elucidate the molecular mechanisms underlying nano-PDT's action in different cancer cell types.
Main Methods:
- Utilized chemodrug-sensitive, intrinsically resistant, and acquired resistant cancer cell models.
- Applied a nanoparticle-based photodynamic therapy approach.
- Analyzed cellular and molecular responses using real-time quantitative PCR array.
Main Results:
- Nano-PDT demonstrated high therapeutic efficiency, effective intracellular delivery, and tumor penetration.
- Nano-PDT achieved significant and indiscriminate therapeutic outcomes in all tested cancer cell types, unlike Temozolomide (TMZ).
- Classical drug resistance pathways were unaffected or downregulated by nano-PDT, which induced apoptosis via downstream genes.
Conclusions:
- Nanoparticulate photodynamic therapy effectively bypasses multiple cancer drug resistance pathways.
- Nano-PDT presents a promising alternative strategy for overcoming therapeutic resistance in cancer treatment.
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