Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB)
The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/12/2778 |
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| author | Michele Moreau Shahinur Acter Lindokuhle M. Ngema Noella Bih Gnagna Sy Lensa S. Keno Kwok Fan Chow Erno Sajo Oscar Nebangwa Jacques Walker Philmo Oh Eric Broyles Wilfred Ngwa Sayeda Yasmin-Karim |
| author_facet | Michele Moreau Shahinur Acter Lindokuhle M. Ngema Noella Bih Gnagna Sy Lensa S. Keno Kwok Fan Chow Erno Sajo Oscar Nebangwa Jacques Walker Philmo Oh Eric Broyles Wilfred Ngwa Sayeda Yasmin-Karim |
| author_sort | Michele Moreau |
| collection | DOAJ |
| description | The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO<sub>2</sub>) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work. |
| first_indexed | 2024-03-08T20:26:27Z |
| format | Article |
| id | doaj.art-dc22af90675f4f07b3fc6e2da4e22b27 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T20:26:27Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-dc22af90675f4f07b3fc6e2da4e22b272023-12-22T14:32:19ZengMDPI AGPharmaceutics1999-49232023-12-011512277810.3390/pharmaceutics15122778Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB)Michele Moreau0Shahinur Acter1Lindokuhle M. Ngema2Noella Bih3Gnagna Sy4Lensa S. Keno5Kwok Fan Chow6Erno Sajo7Oscar Nebangwa8Jacques Walker9Philmo Oh10Eric Broyles11Wilfred Ngwa12Sayeda Yasmin-Karim13Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USADepartment of Radiation Oncology & Molecular Radiation Sciences, Johns’ Hopkins Hospital, Baltimore, MD 21287, USADepartment of Radiation Oncology & Molecular Radiation Sciences, Johns’ Hopkins Hospital, Baltimore, MD 21287, USADepartment of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USADepartment of Radiation Oncology & Molecular Radiation Sciences, Johns’ Hopkins Hospital, Baltimore, MD 21287, USADepartment of Health Administration and Human Resources, The University of Scranton, Scranton, PA 18510, USADepartment of Chemistry and Department of Physics (Medical Physics), University of Massachusetts Lowell, Lowell, MA 01854, USADepartment of Chemistry and Department of Physics (Medical Physics), University of Massachusetts Lowell, Lowell, MA 01854, USANanocan Therapeutics Corporation, Princeton, NJ 08540, USANanocan Therapeutics Corporation, Princeton, NJ 08540, USANanocan Therapeutics Corporation, Princeton, NJ 08540, USANanocan Therapeutics Corporation, Princeton, NJ 08540, USADepartment of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USADepartment of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAThe use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO<sub>2</sub>) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work.https://www.mdpi.com/1999-4923/15/12/2778anti-CD40 monoclonal antibodysmart radiotherapy biomaterialstoxicityhematologyhistopathologyclinical chemistry |
| spellingShingle | Michele Moreau Shahinur Acter Lindokuhle M. Ngema Noella Bih Gnagna Sy Lensa S. Keno Kwok Fan Chow Erno Sajo Oscar Nebangwa Jacques Walker Philmo Oh Eric Broyles Wilfred Ngwa Sayeda Yasmin-Karim Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB) Pharmaceutics anti-CD40 monoclonal antibody smart radiotherapy biomaterials toxicity hematology histopathology clinical chemistry |
| title | Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB) |
| title_full | Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB) |
| title_fullStr | Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB) |
| title_full_unstemmed | Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB) |
| title_short | Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB) |
| title_sort | pre clinical investigations of the pharmacodynamics of immunogenic smart radiotherapy biomaterials isrb |
| topic | anti-CD40 monoclonal antibody smart radiotherapy biomaterials toxicity hematology histopathology clinical chemistry |
| url | https://www.mdpi.com/1999-4923/15/12/2778 |
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