Abstract
Introduction: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors.
Materials and methods: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated.
Results and discussion: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue.
Conclusion: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.
| Language | English |
|---|---|
| Pages | 3553-3570 |
| Number of pages | 18 |
| Journal | International Journal of Nanomedicine |
| Volume | 13 |
| DOIs | |
| Publication status | Published - 19 Jun 2018 |
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Bibliographical note
Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Keywords
- Folic acid targeting
- Photodynamic therapy
- PLGA nanoparticles
- Singlet oxygen generation
- Verteporfin
- X-ray PDT
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X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs. / Clement, Sandhya; Chen, Wenjie; Deng, Wei; Goldys, Ewa M.
In: International Journal of Nanomedicine, Vol. 13, 19.06.2018, p. 3553-3570.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs
AU - Clement, Sandhya
AU - Chen, Wenjie
AU - Deng, Wei
AU - Goldys, Ewa M.
N1 - Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2018/6/19
Y1 - 2018/6/19
N2 - Introduction: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors.Materials and methods: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated.Results and discussion: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue.Conclusion: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.
AB - Introduction: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors.Materials and methods: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated.Results and discussion: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue.Conclusion: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.
KW - Folic acid targeting
KW - Photodynamic therapy
KW - PLGA nanoparticles
KW - Singlet oxygen generation
KW - Verteporfin
KW - X-ray PDT
UR - http://www.scopus.com/inward/record.url?scp=85048820249&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/arc/CE140100003
U2 - 10.2147/IJN.S164967
DO - 10.2147/IJN.S164967
M3 - Article
VL - 13
SP - 3553
EP - 3570
JO - International Journal of Nanomedicine
T2 - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
SN - 1176-9114
ER -