Periodic Reporting for period 1 - BIOnanoPDT (Phthalocyanine-biopolymeric nanoparticle delivery systems for cancer photodynamic therapy)
Période du rapport: 2020-11-02 au 2022-11-01
PUBLICATION 1: Borzęcka W, Domiński A, Kowalczuk M. Recent progress in phthalocyanine-polymeric nanoparticle delivery systems for cancer photodynamic therapy. Nanomaterials. 2021;11(9):2426. doi:10.3390/nano11092426.
1. What is the problem/issue being addressed?
The paper addresses the limitations of conventional cancer treatments (such as chemotherapy, radiotherapy, and surgery), focusing particularly on breast cancer. It highlights the need for more selective, efficient, and less toxic therapeutic strategies. A central issue is the low solubility, aggregation, and lack of targeting of phthalocyanines (Pcs), which are potent photosensitizers used in photodynamic therapy (PDT).
2. Why is it important for society?
Cancer remains one of the leading causes of death globally, with breast cancer being the most common among women. Despite advances in treatment, current therapies still have severe side effects and limitations. Developing safer, more targeted, and effective treatments like nanoparticle-based PDT could significantly improve survival rates and quality of life for cancer patients, addressing a major public health challenge.
3. What are the overall objectives?
The objective is to review the development of phthalocyanine-loaded polymeric nanoparticles that are:
• pH-sensitive to exploit the acidic tumor environment,
• capable of delivering Pcs selectively to tumor cells,
• enhanced in solubility, photostability, and therapeutic effect in PDT applications.
Ultimately, the goal is to review an advanced drug delivery systems for more effective and selective treatment of breast cancer through photodynamic therapy.
PUBLICATION 2: Malarz K, Borzęcka W, Ziola P, Domiński A, Rawicka P, Bialik-Wąs K, Kurcok P, Torres T, Mrozek-Wilczkiewicz A. pH-sensitive phthalocyanine-loaded polymeric nanoparticles as a novel treatment strategy for breast cancer. Bioorg Chem. 2025;155:108127. doi:10.1016/j.bioorg.2025.108127.
1. What is the problem/issue being addressed?
The study addresses the limited effectiveness and high toxicity of conventional breast cancer treatments, as well as the poor solubility and low tumor-targeting ability of traditional photosensitizers used in photodynamic therapy (PDT). The researchers aim to improve the delivery and therapeutic efficacy of phthalocyanine-based PDT agents by encapsulating them in pH-sensitive polymeric nanoparticles.
2. Why is it important for society?
Breast cancer is one of the most common and deadly cancers worldwide, particularly among women. Current treatments often have serious side effects and limited effectiveness, especially in HER-2 positive or drug-resistant cancers. Developing targeted, less toxic, and more efficient therapies like nanoparticle-based PDT could significantly improve patient outcomes, reduce side effects, and increase the quality of life for those affected by breast cancer.
3. What are the overall objectives?
The main objectives of the study are to:
-Design and synthesize pH-sensitive polymeric micelles that encapsulate phthalocyanine-based photosensitizers (Pc4 and TT1),
-Improve their solubility, photostability, and tumor selectivity,
-Test their anticancer activity in vitro, focusing on breast cancer cell lines, especially HER-2 positive ones,
-Investigate their mechanism of action, including ROS generation, subcellular localization, and influence on signaling pathways related to apoptosis and cancer cell survival.
1. What is the problem/issue being addressed?
The paper addresses the limitations of conventional cancer treatments (such as chemotherapy, radiotherapy, and surgery), focusing particularly on breast cancer. It highlights the need for more selective, efficient, and less toxic therapeutic strategies. A central issue is the low solubility, aggregation, and lack of targeting of phthalocyanines (Pcs), which are potent photosensitizers used in photodynamic therapy (PDT).
2. Why is it important for society?
Cancer remains one of the leading causes of death globally, with breast cancer being the most common among women. Despite advances in treatment, current therapies still have severe side effects and limitations. Developing safer, more targeted, and effective treatments like nanoparticle-based PDT could significantly improve survival rates and quality of life for cancer patients, addressing a major public health challenge.
3. What are the overall objectives?
The objective is to review the development of phthalocyanine-loaded polymeric nanoparticles that are:
• pH-sensitive to exploit the acidic tumor environment,
• capable of delivering Pcs selectively to tumor cells,
• enhanced in solubility, photostability, and therapeutic effect in PDT applications.
Ultimately, the goal is to review an advanced drug delivery systems for more effective and selective treatment of breast cancer through photodynamic therapy.
PUBLICATION 2: Malarz K, Borzęcka W, Ziola P, Domiński A, Rawicka P, Bialik-Wąs K, Kurcok P, Torres T, Mrozek-Wilczkiewicz A. pH-sensitive phthalocyanine-loaded polymeric nanoparticles as a novel treatment strategy for breast cancer. Bioorg Chem. 2025;155:108127. doi:10.1016/j.bioorg.2025.108127.
1. What is the problem/issue being addressed?
The study addresses the limited effectiveness and high toxicity of conventional breast cancer treatments, as well as the poor solubility and low tumor-targeting ability of traditional photosensitizers used in photodynamic therapy (PDT). The researchers aim to improve the delivery and therapeutic efficacy of phthalocyanine-based PDT agents by encapsulating them in pH-sensitive polymeric nanoparticles.
2. Why is it important for society?
Breast cancer is one of the most common and deadly cancers worldwide, particularly among women. Current treatments often have serious side effects and limited effectiveness, especially in HER-2 positive or drug-resistant cancers. Developing targeted, less toxic, and more efficient therapies like nanoparticle-based PDT could significantly improve patient outcomes, reduce side effects, and increase the quality of life for those affected by breast cancer.
3. What are the overall objectives?
The main objectives of the study are to:
-Design and synthesize pH-sensitive polymeric micelles that encapsulate phthalocyanine-based photosensitizers (Pc4 and TT1),
-Improve their solubility, photostability, and tumor selectivity,
-Test their anticancer activity in vitro, focusing on breast cancer cell lines, especially HER-2 positive ones,
-Investigate their mechanism of action, including ROS generation, subcellular localization, and influence on signaling pathways related to apoptosis and cancer cell survival.
Work performed in the article: Malarz K, Borzęcka W, Ziola P, Domiński A, Rawicka P, Bialik-Wąs K, Kurcok P, Torres T, Mrozek-Wilczkiewicz A. pH-sensitive phthalocyanine-loaded polymeric nanoparticles as a novel treatment strategy for breast cancer. Bioorg Chem. 2025;155:108127. doi:10.1016/j.bioorg.2025.108127. and main results achieved so far
Work performed:
• Designed and synthesized pH-sensitive polymeric micelles loaded with two photosensitizers: Pc4 and TT1, both phthalocyanine derivatives.
• These micelles were optimized for stability, pH-triggered drug release, and enhanced photodynamic activity.
• A full spectrum of in vitro studies was performed, including:
o Characterization of micelle size, structure, and drug release under acidic conditions,
o Cytotoxicity and photocytotoxicity tests on breast cancer and other cancer cell lines,
o ROS generation assays, including singlet oxygen quantum yield,
o Cellular uptake and subcellular localization,
o Apoptosis induction (Annexin V assay),
o Western blot analysis for key signaling proteins (Akt, p-Akt, BID, HO-1, GLUT1, ERK).
Main results achieved:
• Encapsulation significantly improved efficacy and selectivity:
o Pc4- and TT1-loaded nanoparticles had much lower IC50 values than their free forms.
o SK-BR-3 breast cancer cells were most responsive (Pc4-NPs IC50 = 0.021 μM).
• High ROS production was confirmed both in solution and in cancer cells.
• Subcellular localization showed preferential accumulation in lysosomes.
• Both nanoparticles induced apoptosis effectively at lower concentrations than free drugs.
• Western blotting revealed inhibition of key survival signaling pathways, notably Akt and its phosphorylated form, suggesting mechanisms of enhanced cytotoxicity.
• The systems were non-toxic without light activation (dark cytotoxicity), showing suitability for photodynamic therapy (PDT).
Work performed:
• Designed and synthesized pH-sensitive polymeric micelles loaded with two photosensitizers: Pc4 and TT1, both phthalocyanine derivatives.
• These micelles were optimized for stability, pH-triggered drug release, and enhanced photodynamic activity.
• A full spectrum of in vitro studies was performed, including:
o Characterization of micelle size, structure, and drug release under acidic conditions,
o Cytotoxicity and photocytotoxicity tests on breast cancer and other cancer cell lines,
o ROS generation assays, including singlet oxygen quantum yield,
o Cellular uptake and subcellular localization,
o Apoptosis induction (Annexin V assay),
o Western blot analysis for key signaling proteins (Akt, p-Akt, BID, HO-1, GLUT1, ERK).
Main results achieved:
• Encapsulation significantly improved efficacy and selectivity:
o Pc4- and TT1-loaded nanoparticles had much lower IC50 values than their free forms.
o SK-BR-3 breast cancer cells were most responsive (Pc4-NPs IC50 = 0.021 μM).
• High ROS production was confirmed both in solution and in cancer cells.
• Subcellular localization showed preferential accumulation in lysosomes.
• Both nanoparticles induced apoptosis effectively at lower concentrations than free drugs.
• Western blotting revealed inhibition of key survival signaling pathways, notably Akt and its phosphorylated form, suggesting mechanisms of enhanced cytotoxicity.
• The systems were non-toxic without light activation (dark cytotoxicity), showing suitability for photodynamic therapy (PDT).
1. Progress beyond the state of the art
This project presents a significant advancement in cancer photodynamic therapy (PDT) by developing pH-sensitive polymeric nanoparticles (NPs) loaded with phthalocyanine-based photosensitizers (Pc4 and TT1). Unlike conventional photosensitizers, these NPs:
• Show enhanced tumor targeting and cellular uptake in acidic environments typical of tumors,
• Demonstrate superior phototoxicity and selectivity toward HER2-positive breast cancer cells (especially SK-BR-3),
• Maintain low dark cytotoxicity, meaning they are non-toxic until activated by light,
• Are capable of targeted ROS generation, particularly singlet oxygen (^1O2), which leads to apoptosis.
These advances address major limitations of older photosensitizers, such as poor solubility, aggregation, and low tumor selectivity.
2. Expected results until the end of the project
• Further in vivo testing to evaluate biodistribution, pharmacokinetics, and therapeutic efficacy in animal models.
• Application to more aggressive cancer types, such as triple-negative breast cancer (TNBC), which lacks effective targeted treatments.
• Development of multifunctional delivery platforms (e.g. combining photodynamic therapy with chemotherapy or immunotherapy).
• Optimization of drug release profiles for controlled, site-specific therapy.
3. Potential impacts
a. Scientific impact:
• Provides a novel platform for photodynamic therapy with improved delivery and efficacy.
• Enhances understanding of ROS-mediated apoptosis mechanisms in HER2-positive cancers.
• Opens new avenues for nanoparticle-based combination therapies.
b. Socio-economic and societal implications:
• Potential to reduce treatment costs and hospital stays by improving therapeutic precision and minimizing side effects.
• Offers a less invasive, more tolerable alternative to conventional chemotherapy.
• May lead to new treatment protocols for resistant or recurrent breast cancer, improving long-term survival and quality of life.
This project presents a significant advancement in cancer photodynamic therapy (PDT) by developing pH-sensitive polymeric nanoparticles (NPs) loaded with phthalocyanine-based photosensitizers (Pc4 and TT1). Unlike conventional photosensitizers, these NPs:
• Show enhanced tumor targeting and cellular uptake in acidic environments typical of tumors,
• Demonstrate superior phototoxicity and selectivity toward HER2-positive breast cancer cells (especially SK-BR-3),
• Maintain low dark cytotoxicity, meaning they are non-toxic until activated by light,
• Are capable of targeted ROS generation, particularly singlet oxygen (^1O2), which leads to apoptosis.
These advances address major limitations of older photosensitizers, such as poor solubility, aggregation, and low tumor selectivity.
2. Expected results until the end of the project
• Further in vivo testing to evaluate biodistribution, pharmacokinetics, and therapeutic efficacy in animal models.
• Application to more aggressive cancer types, such as triple-negative breast cancer (TNBC), which lacks effective targeted treatments.
• Development of multifunctional delivery platforms (e.g. combining photodynamic therapy with chemotherapy or immunotherapy).
• Optimization of drug release profiles for controlled, site-specific therapy.
3. Potential impacts
a. Scientific impact:
• Provides a novel platform for photodynamic therapy with improved delivery and efficacy.
• Enhances understanding of ROS-mediated apoptosis mechanisms in HER2-positive cancers.
• Opens new avenues for nanoparticle-based combination therapies.
b. Socio-economic and societal implications:
• Potential to reduce treatment costs and hospital stays by improving therapeutic precision and minimizing side effects.
• Offers a less invasive, more tolerable alternative to conventional chemotherapy.
• May lead to new treatment protocols for resistant or recurrent breast cancer, improving long-term survival and quality of life.