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Updated: Oct 22, 2025
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Pheophorbide A and Paclitaxel Bioresponsive Nanoparticles as Double-Punch Platform for Cancer Therapy
Francesca Moret1, Luca Menilli1, Manuele Battan2
1Department of Biology, University of Padova, 35100 Padova, Italy.
Abstract:
Cancer therapy is still a challenging issue. To address this, the combination of anticancer drugs with other therapeutic modalities, such as light-triggered therapies, has emerged as a promising approach, primarily when both active ingredients are provided within a single nanosystem. Herein, we describe the unprecedented preparation of tumor microenvironment (TME) responsive nanoparticles exclusively composed of a paclitaxel (PTX) prodrug and the photosensitizer pheophorbide A (PheoA), e.g., PheoA≅PTX2S. This system aimed to achieve both the TME-triggered and controlled release of PTX and the synergistic/additive effect by PheoA-mediated photodynamic therapy. PheoA≅PTX2S were produced in a simple one-pot process, exhibiting excellent reproducibility, stability, and the ability to load up to 100% PTX and 40% of PheoA. Exposure of PheoA≅PTX2S nanoparticles to TME-mimicked environment provided fast disassembly compared to normal conditions, leading to PTX and PheoA release and consequently elevated cytotoxicity. Our data indicate that PheoA incorporation into nanoparticles prevents its aggregation, thus providing a greater extent of ROS and singlet oxygen production. Importantly, in SK-OV-3 cells, PheoA≅PTX2S allowed a 30-fold PTX dose reduction and a 3-fold dose reduction of PheoA. Our data confirm that prodrug-based nanocarriers represent valuable and sustainable drug delivery systems, possibly reducing toxicity and expediting preclinical and clinical translation.
Insights
Researchers developed novel nanoparticles combining paclitaxel (PTX) and pheophorbide A (PheoA) for enhanced cancer therapy. These tumor microenvironment-responsive systems enable controlled drug release and photodynamic therapy, reducing required drug doses.
Area of Science:
- Nanomedicine
- Photodynamic Therapy
- Drug Delivery Systems
Background:
- Cancer therapy faces challenges, necessitating innovative treatment strategies.
- Combination therapies, particularly light-triggered approaches within nanosystems, show promise.
- Developing responsive nanocarriers for controlled drug release is crucial.
Purpose of the Study:
- To create tumor microenvironment (TME)-responsive nanoparticles for combined chemotherapy and photodynamic therapy.
- To develop a nanosystem exclusively from a paclitaxel (PTX) prodrug and pheophorbide A (PheoA).
- To evaluate the TME-triggered release, stability, and efficacy of the PheoA≅PTX2S nanosystem.
Main Methods:
- A one-pot synthesis process for PheoA≅PTX2S nanoparticles.
- Assessment of nanoparticle stability and drug loading capacity (100% PTX, 40% PheoA).
- Evaluation of nanoparticle disassembly and drug release in TME-mimicked conditions versus normal conditions.
Main Results:
- PheoA≅PTX2S nanoparticles demonstrated high reproducibility, stability, and drug loading.
- Exposure to TME-mimicked conditions induced rapid nanoparticle disassembly and release of PTX and PheoA.
- PheoA incorporation prevented aggregation, enhancing reactive oxygen species (ROS) and singlet oxygen production.
- Significant dose reduction observed: 30-fold for PTX and 3-fold for PheoA in SK-OV-3 cells.
Conclusions:
- Prodrug-based nanocarriers are effective and sustainable drug delivery systems.
- The developed PheoA≅PTX2S nanoparticles offer controlled release and synergistic therapeutic effects.
- This approach has the potential to reduce drug toxicity and accelerate clinical translation for cancer therapy.
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