Boosted Radiation Bystander Effect of PSMA-Targeted Gold Nanoparticles in Prostate Cancer Radiosensitization
Metal nanoparticles are effective radiosensitizers that locally enhance radiation doses in targeted cancer cells. Compared with other metal nanoparticles, gold nanoparticles (GNPs) exhibit high biocompatibility, low toxicity, and they increase secondary electron scatter. Herein, we investigated the...
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MDPI AG
2022-12-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/12/24/4440 |
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| author | Daiki Hara Wensi Tao Ryder M. Schmidt Yu-Ping Yang Sylvia Daunert Nesrin Dogan John Chetley Ford Alan Pollack Junwei Shi |
| author_facet | Daiki Hara Wensi Tao Ryder M. Schmidt Yu-Ping Yang Sylvia Daunert Nesrin Dogan John Chetley Ford Alan Pollack Junwei Shi |
| author_sort | Daiki Hara |
| collection | DOAJ |
| description | Metal nanoparticles are effective radiosensitizers that locally enhance radiation doses in targeted cancer cells. Compared with other metal nanoparticles, gold nanoparticles (GNPs) exhibit high biocompatibility, low toxicity, and they increase secondary electron scatter. Herein, we investigated the effects of active-targeting GNPs on the radiation-induced bystander effect (RIBE) in prostate cancer cells. The impact of GNPs on the RIBE presents implications for secondary cancers or spatially fractionated radiotherapy treatments. Anti-prostate-specific membrane antigen (PSMA) antibodies were conjugated with PEGylated GNPs through EDC–NHS chemistry. The media transfer technique was performed to induce the RIBE on the non-irradiated bystander cells. This study focused on the LNCaP cell line, because it can model a wide range of stages relating to prostate cancer progression, including the transition from androgen dependence to castration resistance and bone metastasis. First, LNCaP cells were pretreated with phosphate buffered saline (PBS) or PSMA-targeted GNPs (PGNPs) for 24 h and irradiated with 160 kVp X-rays (0–8 Gy). Following that, the collected culture media were filtered (sterile 0.45 µm polyethersulfone) in order to acquire PBS- and PGNP- conditioned media (CM). Then, PBS- and PGNP-CM were transferred to the bystander cells that were loaded with/without PGNPs. MTT, γ-H2AX, clonogenic assays and reactive oxygen species assessments were performed to compare RIBE responses under different treatments. Compared with 2 Gy-PBS-CM, 8 Gy-PBS-CM demonstrated a much higher RIBE response, thus validating the dose dependence of RIBE in LNCaP cells. Compared with PBS-CM, PGNP-CM exhibited lower cell viability, higher DNA damage, and a smaller survival fraction. In the presence of PBS-CM, bystander cells loaded with PGNPs showed increased cell death compared with cells that did not have PGNPs. These results demonstrate the PGNP-boosted expression and sensitivity of RIBE in prostate cancer cells. |
| first_indexed | 2024-03-09T16:01:44Z |
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| id | doaj.art-dbbd367be14b41738e00c4f715684e17 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-09T16:01:44Z |
| publishDate | 2022-12-01 |
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| series | Nanomaterials |
| spelling | doaj.art-dbbd367be14b41738e00c4f715684e172023-11-24T17:04:24ZengMDPI AGNanomaterials2079-49912022-12-011224444010.3390/nano12244440Boosted Radiation Bystander Effect of PSMA-Targeted Gold Nanoparticles in Prostate Cancer RadiosensitizationDaiki Hara0Wensi Tao1Ryder M. Schmidt2Yu-Ping Yang3Sylvia Daunert4Nesrin Dogan5John Chetley Ford6Alan Pollack7Junwei Shi8Department of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USASylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USASylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USAMetal nanoparticles are effective radiosensitizers that locally enhance radiation doses in targeted cancer cells. Compared with other metal nanoparticles, gold nanoparticles (GNPs) exhibit high biocompatibility, low toxicity, and they increase secondary electron scatter. Herein, we investigated the effects of active-targeting GNPs on the radiation-induced bystander effect (RIBE) in prostate cancer cells. The impact of GNPs on the RIBE presents implications for secondary cancers or spatially fractionated radiotherapy treatments. Anti-prostate-specific membrane antigen (PSMA) antibodies were conjugated with PEGylated GNPs through EDC–NHS chemistry. The media transfer technique was performed to induce the RIBE on the non-irradiated bystander cells. This study focused on the LNCaP cell line, because it can model a wide range of stages relating to prostate cancer progression, including the transition from androgen dependence to castration resistance and bone metastasis. First, LNCaP cells were pretreated with phosphate buffered saline (PBS) or PSMA-targeted GNPs (PGNPs) for 24 h and irradiated with 160 kVp X-rays (0–8 Gy). Following that, the collected culture media were filtered (sterile 0.45 µm polyethersulfone) in order to acquire PBS- and PGNP- conditioned media (CM). Then, PBS- and PGNP-CM were transferred to the bystander cells that were loaded with/without PGNPs. MTT, γ-H2AX, clonogenic assays and reactive oxygen species assessments were performed to compare RIBE responses under different treatments. Compared with 2 Gy-PBS-CM, 8 Gy-PBS-CM demonstrated a much higher RIBE response, thus validating the dose dependence of RIBE in LNCaP cells. Compared with PBS-CM, PGNP-CM exhibited lower cell viability, higher DNA damage, and a smaller survival fraction. In the presence of PBS-CM, bystander cells loaded with PGNPs showed increased cell death compared with cells that did not have PGNPs. These results demonstrate the PGNP-boosted expression and sensitivity of RIBE in prostate cancer cells.https://www.mdpi.com/2079-4991/12/24/4440gold nanoparticleradiosensitizationradiation-induced bystander effectprostate LNCaP cancer cellsprostate-specific membrane antigenactive targeting |
| spellingShingle | Daiki Hara Wensi Tao Ryder M. Schmidt Yu-Ping Yang Sylvia Daunert Nesrin Dogan John Chetley Ford Alan Pollack Junwei Shi Boosted Radiation Bystander Effect of PSMA-Targeted Gold Nanoparticles in Prostate Cancer Radiosensitization Nanomaterials gold nanoparticle radiosensitization radiation-induced bystander effect prostate LNCaP cancer cells prostate-specific membrane antigen active targeting |
| title | Boosted Radiation Bystander Effect of PSMA-Targeted Gold Nanoparticles in Prostate Cancer Radiosensitization |
| title_full | Boosted Radiation Bystander Effect of PSMA-Targeted Gold Nanoparticles in Prostate Cancer Radiosensitization |
| title_fullStr | Boosted Radiation Bystander Effect of PSMA-Targeted Gold Nanoparticles in Prostate Cancer Radiosensitization |
| title_full_unstemmed | Boosted Radiation Bystander Effect of PSMA-Targeted Gold Nanoparticles in Prostate Cancer Radiosensitization |
| title_short | Boosted Radiation Bystander Effect of PSMA-Targeted Gold Nanoparticles in Prostate Cancer Radiosensitization |
| title_sort | boosted radiation bystander effect of psma targeted gold nanoparticles in prostate cancer radiosensitization |
| topic | gold nanoparticle radiosensitization radiation-induced bystander effect prostate LNCaP cancer cells prostate-specific membrane antigen active targeting |
| url | https://www.mdpi.com/2079-4991/12/24/4440 |
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