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Androgen receptor targeted conjugate for bimodal photodynamic therapy of prostate cancer in vitro
- Source :
- Bioconjugate chemistry 26 (2015): 1662–1671. doi:10.1021/acs.bioconjchem.5b00261, info:cnr-pdr/source/autori:Rapozzi, Valentina; Ragno, Daniele; Guerrini, Andrea; Ferroni, Claudia; Pietra, Emilia Della; Cesselli, Daniela; Castoria, Gabriella; Di Donato, Marzia; Saracino, Emanuela; Benfenati, Valentina; Varchi, Greta/titolo:Androgen Receptor Targeted Conjugate for Bimodal Photodynamic Therapy of Prostate Cancer in Vitro/doi:10.1021%2Facs.bioconjchem.5b00261/rivista:Bioconjugate chemistry/anno:2015/pagina_da:1662/pagina_a:1671/intervallo_pagine:1662–1671/volume:26
- Publication Year :
- 2015
-
Abstract
- Prostate cancer (PC) represents the most common type of cancer among males and is the second leading cause of cancer death in men in Western society. Current options for PC therapy remain unsatisfactory, since they often produce uncomfortable long-term side effects, such as impotence (70%) and incontinence (5–20%) even in the first stages of the disease. Light-triggered therapies, such as photodynamic therapy, have the potential to provide important advances in the treatment of localized and partially metastasized prostate cancer. We have designed a novel molecular conjugate (DR2) constituted of a photosensitizer (pheophorbide a, Pba), connected to a nonsteroidal anti-androgen molecule through a small pegylated linker. This study aims at investigating whether DR2 represents a valuable approach for PC treatment based on light-induced production of single oxygen and nitric oxide (NO) in vitro. Besides being able to efficiently bind the androgen receptor (AR), the 2-trifluoromethylnitrobenzene ring on the DR2 backbone is able to release cytotoxic NO under the exclusive control of light, thus augmenting the general photodynamic effect. Although DR2 is similarly internalized in cells expressing different levels of androgen receptor, the AR ligand prevents its efflux through the ABCG2-pump. In vitro phototoxicity experiments demonstrated the ability of DR2 to kill cancer cells more efficiently than Pba, while no dark toxicity was observed. Overall, the presented approach is very promising for further development of AR-photosensitizer conjugates in the multimodal photodynamic treatment of prostate cancer.
- Subjects :
- Chlorophyll
Male
medicine.medical_specialty
medicine.medical_treatment
Biomedical Engineering
Pharmaceutical Science
Photodynamic therapy
Bioengineering
Antineoplastic Agents
In Vitro Techniques
NO
Androgen
Targeted therapy
Prostate cancer
chemistry.chemical_compound
PDT
Internal medicine
Receptors
medicine
Tumor Cells, Cultured
Humans
Photosensitizer
Pharmacology
Cultured
Photosensitizing Agents
business.industry
Medicine (all)
Organic Chemistry
Cancer
Prostatic Neoplasms
Androgen Antagonists
medicine.disease
In vitro
Tumor Cells
Androgen receptor
Receptors, Androgen
Photochemotherapy
Biotechnology
3003
Endocrinology
chemistry
photodynamic therapy
Pheophorbide A
Cancer research
business
Conjugate
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Bioconjugate chemistry 26 (2015): 1662–1671. doi:10.1021/acs.bioconjchem.5b00261, info:cnr-pdr/source/autori:Rapozzi, Valentina; Ragno, Daniele; Guerrini, Andrea; Ferroni, Claudia; Pietra, Emilia Della; Cesselli, Daniela; Castoria, Gabriella; Di Donato, Marzia; Saracino, Emanuela; Benfenati, Valentina; Varchi, Greta/titolo:Androgen Receptor Targeted Conjugate for Bimodal Photodynamic Therapy of Prostate Cancer in Vitro/doi:10.1021%2Facs.bioconjchem.5b00261/rivista:Bioconjugate chemistry/anno:2015/pagina_da:1662/pagina_a:1671/intervallo_pagine:1662–1671/volume:26
- Accession number :
- edsair.doi.dedup.....35073c4ea911fdd1659917f8ffed94fa