ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation
Abstract Prostate cancer (PCa) is one of the fatal illnesses among males globally. PCa-treatment does not include radiotherapy. Chemotherapy eventually causes drug resistance, disease recurrence, metastatic advancement, multi-organ failure, and death. Preclinical data on PCa-induced by carcinogens a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Cancer Nanotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12645-023-00223-5 |
| _version_ | 1797578202051248128 |
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| author | Ashique Al Hoque Debasmita Dutta Brahamacharry Paul Leena Kumari Iman Ehsan Moumita Dhara Biswajit Mukherjee Mohiuddin Quadir Benny Abraham Kaipparettu Soumik Laha Shantanu Ganguly |
| author_facet | Ashique Al Hoque Debasmita Dutta Brahamacharry Paul Leena Kumari Iman Ehsan Moumita Dhara Biswajit Mukherjee Mohiuddin Quadir Benny Abraham Kaipparettu Soumik Laha Shantanu Ganguly |
| author_sort | Ashique Al Hoque |
| collection | DOAJ |
| description | Abstract Prostate cancer (PCa) is one of the fatal illnesses among males globally. PCa-treatment does not include radiotherapy. Chemotherapy eventually causes drug resistance, disease recurrence, metastatic advancement, multi-organ failure, and death. Preclinical data on PCa-induced by carcinogens are truly scarce. Although some data on xenograft-PCa in animals are available, they mostly belonged to immuno-compromised animals. Here, we developed ΔPSap4#5 aptamer surface-functionalized abiraterone-loaded biodegradable nanoparticle (Apt-ABR-NP) to investigate its targeting ability to prostate-specific membrane antigen (PSMA) in carcinogen-induced PCa mice and the therapeutic efficacy of the formulation. Aptamers are called synthetic monoclonal antibodies for their target specificity. However, they are devoid of the toxicity problem generally associated with the antibody. Abiraterone is a testosterone and androgen inhibitor, a new drug molecule that shows good therapeutic efficacy in PCa. The developed nanoparticles were physicochemically characterized and used for various in vitro and in vivo investigations. Nanoparticles had an average size of 149 nm with sustained drug release that followed Korsmeyer–Peppas kinetics. In vitro investigation showed that Apt-ABR-NP produced 87.4% apoptotic cells and 95.3% loss of mitochondrial membrane potential in LNCaP cells after 48 h of incubation. In vivo gamma scintigraphy, live imaging, and biodistribution studies in prostate cancer animal models showed the predominant targeting potential of Apt-ABR-NP. Histopathological investigation showed the remarkable therapeutic efficacy of the formulation. The pharmacokinetic study showed an increased biological half-life and enhanced blood residence time of Apt-ABR-NP. Apt-ABR-NP therapy can thus minimize off-target cytotoxicity, reduce drug loss due to site-specific delivery, and deliver abiraterone in a sustained manner to the organ of interest. Thus, the present study brings new hope for better therapeutic management of PCa in the near future. Graphical Abstract |
| first_indexed | 2024-03-10T22:18:45Z |
| format | Article |
| id | doaj.art-d0d8145a49bf41a89be3af69103b9019 |
| institution | Directory Open Access Journal |
| issn | 1868-6958 1868-6966 |
| language | English |
| last_indexed | 2024-03-10T22:18:45Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Nanotechnology |
| spelling | doaj.art-d0d8145a49bf41a89be3af69103b90192023-11-19T12:22:02ZengBMCCancer Nanotechnology1868-69581868-69662023-09-0114113410.1186/s12645-023-00223-5ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigationAshique Al Hoque0Debasmita Dutta1Brahamacharry Paul2Leena Kumari3Iman Ehsan4Moumita Dhara5Biswajit Mukherjee6Mohiuddin Quadir7Benny Abraham Kaipparettu8Soumik Laha9Shantanu Ganguly10Department of Pharmaceutical Technology, Jadavpur UniversityDepartment of Coatings and Polymeric Materials, North Dakota State UniversityDepartment of Pharmaceutical Technology, Jadavpur UniversityDepartment of Pharmaceutical Technology, Jadavpur UniversityDepartment of Pharmaceutical Technology, Jadavpur UniversityDepartment of Pharmaceutical Technology, Jadavpur UniversityDepartment of Pharmaceutical Technology, Jadavpur UniversityDepartment of Coatings and Polymeric Materials, North Dakota State UniversityDepartment of Molecular and Human Genetics, Baylor College of MedicineCSIR-Indian Institute of Chemical BiologyRegional Radiation Medicine Center, Thakurpukur Cancer Center, and Welfare Home CampusAbstract Prostate cancer (PCa) is one of the fatal illnesses among males globally. PCa-treatment does not include radiotherapy. Chemotherapy eventually causes drug resistance, disease recurrence, metastatic advancement, multi-organ failure, and death. Preclinical data on PCa-induced by carcinogens are truly scarce. Although some data on xenograft-PCa in animals are available, they mostly belonged to immuno-compromised animals. Here, we developed ΔPSap4#5 aptamer surface-functionalized abiraterone-loaded biodegradable nanoparticle (Apt-ABR-NP) to investigate its targeting ability to prostate-specific membrane antigen (PSMA) in carcinogen-induced PCa mice and the therapeutic efficacy of the formulation. Aptamers are called synthetic monoclonal antibodies for their target specificity. However, they are devoid of the toxicity problem generally associated with the antibody. Abiraterone is a testosterone and androgen inhibitor, a new drug molecule that shows good therapeutic efficacy in PCa. The developed nanoparticles were physicochemically characterized and used for various in vitro and in vivo investigations. Nanoparticles had an average size of 149 nm with sustained drug release that followed Korsmeyer–Peppas kinetics. In vitro investigation showed that Apt-ABR-NP produced 87.4% apoptotic cells and 95.3% loss of mitochondrial membrane potential in LNCaP cells after 48 h of incubation. In vivo gamma scintigraphy, live imaging, and biodistribution studies in prostate cancer animal models showed the predominant targeting potential of Apt-ABR-NP. Histopathological investigation showed the remarkable therapeutic efficacy of the formulation. The pharmacokinetic study showed an increased biological half-life and enhanced blood residence time of Apt-ABR-NP. Apt-ABR-NP therapy can thus minimize off-target cytotoxicity, reduce drug loss due to site-specific delivery, and deliver abiraterone in a sustained manner to the organ of interest. Thus, the present study brings new hope for better therapeutic management of PCa in the near future. Graphical Abstracthttps://doi.org/10.1186/s12645-023-00223-5Aptamer-mediated tumor targetingProstate-specific membrane antigen (PSMA)Abiraterone acetateProstate cancer therapyPharmacokinetics |
| spellingShingle | Ashique Al Hoque Debasmita Dutta Brahamacharry Paul Leena Kumari Iman Ehsan Moumita Dhara Biswajit Mukherjee Mohiuddin Quadir Benny Abraham Kaipparettu Soumik Laha Shantanu Ganguly ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation Cancer Nanotechnology Aptamer-mediated tumor targeting Prostate-specific membrane antigen (PSMA) Abiraterone acetate Prostate cancer therapy Pharmacokinetics |
| title | ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation |
| title_full | ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation |
| title_fullStr | ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation |
| title_full_unstemmed | ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation |
| title_short | ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation |
| title_sort | δpsap4 5 surface functionalized abiraterone loaded nanoparticle successfully inhibits carcinogen induced prostate cancer in mice a mechanistic investigation |
| topic | Aptamer-mediated tumor targeting Prostate-specific membrane antigen (PSMA) Abiraterone acetate Prostate cancer therapy Pharmacokinetics |
| url | https://doi.org/10.1186/s12645-023-00223-5 |
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