Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy

João A Oshiro-Junior, Mariana Rillo Sato, Fernanda Isadora Boni, Karen Loraine Macena Santos, Kleber Thiago de Oliveira, Laura Marise de Freitas, Carla Raquel Fontana, Dean Nicholas, Anthony P. McHale, J Callan, Marlus Chorilli

Research output: Contribution to journalArticle

Abstract

Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ± 0.58% and 27.7 ± 3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 μM of PS present non-toxic with >80 ± 6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ± 4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.
LanguageEnglish
Number of pages7
JournalMaterials Science and Engineering: C
Volume108
Issue number110462
Early online date23 Nov 2019
DOIs
Publication statusE-pub ahead of print - 23 Nov 2019

Fingerprint

folic acid
Photodynamic therapy
Photosensitizing Agents
Photosensitizers
Folic Acid
Lipids
lipids
therapy
Acids
breast
cancer
oxygen
castor oil
public health
stearates
causes
chemotherapy
phthalocyanine
viability
death

Keywords

  • Nanostructured lipid carriers; Functionalization; Folic acid; Phthalocyanines; Photodynamic therapy; Breast cancer
  • Nanostructured lipid carriers
  • Photodynamic therapy
  • Functionalization
  • Breast cancer
  • Folic acid
  • Phthalocyanines

Cite this

Oshiro-Junior, J. A., Rillo Sato, M., Isadora Boni, F., Macena Santos, K. L., Thiago de Oliveira, K., Marise de Freitas, L., ... Chorilli, M. (2020). Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy. Materials Science and Engineering: C, 108(110462). https://doi.org/10.1016/j.msec.2019.110462
Oshiro-Junior, João A ; Rillo Sato, Mariana ; Isadora Boni, Fernanda ; Macena Santos, Karen Loraine ; Thiago de Oliveira, Kleber ; Marise de Freitas, Laura ; Raquel Fontana, Carla ; Nicholas, Dean ; McHale, Anthony P. ; Callan, J ; Chorilli, Marlus. / Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy. In: Materials Science and Engineering: C. 2020 ; Vol. 108, No. 110462.
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abstract = "Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ± 0.58{\%} and 27.7 ± 3.16{\%} after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 μM of PS present non-toxic with >80 ± 6.8{\%} viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ± 4{\%}). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.",
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Oshiro-Junior, JA, Rillo Sato, M, Isadora Boni, F, Macena Santos, KL, Thiago de Oliveira, K, Marise de Freitas, L, Raquel Fontana, C, Nicholas, D, McHale, AP, Callan, J & Chorilli, M 2020, 'Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy', Materials Science and Engineering: C, vol. 108, no. 110462. https://doi.org/10.1016/j.msec.2019.110462

Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy. / Oshiro-Junior, João A; Rillo Sato, Mariana; Isadora Boni, Fernanda; Macena Santos, Karen Loraine; Thiago de Oliveira, Kleber; Marise de Freitas, Laura; Raquel Fontana, Carla; Nicholas, Dean; McHale, Anthony P.; Callan, J; Chorilli, Marlus.

In: Materials Science and Engineering: C, Vol. 108, No. 110462, 31.03.2020.

Research output: Contribution to journalArticle

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T1 - Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy

AU - Oshiro-Junior, João A

AU - Rillo Sato, Mariana

AU - Isadora Boni, Fernanda

AU - Macena Santos, Karen Loraine

AU - Thiago de Oliveira, Kleber

AU - Marise de Freitas, Laura

AU - Raquel Fontana, Carla

AU - Nicholas, Dean

AU - McHale, Anthony P.

AU - Callan, J

AU - Chorilli, Marlus

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N2 - Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ± 0.58% and 27.7 ± 3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 μM of PS present non-toxic with >80 ± 6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ± 4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.

AB - Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ± 0.58% and 27.7 ± 3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 μM of PS present non-toxic with >80 ± 6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ± 4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.

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KW - Photodynamic therapy

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KW - Folic acid

KW - Phthalocyanines

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Oshiro-Junior JA, Rillo Sato M, Isadora Boni F, Macena Santos KL, Thiago de Oliveira K, Marise de Freitas L et al. Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy. Materials Science and Engineering: C. 2020 Mar 31;108(110462). https://doi.org/10.1016/j.msec.2019.110462