PUBLICATION
PSMA-targeted combination brusatol and docetaxel nanotherapeutics for the treatment of prostate cancer
- Authors
- Adekiya, T.A., Hudson, T., Bakare, O., Ameyaw, E.E., Adebayo, A., Olajubutu, O., Adesina, S.K.
- ID
- ZDB-PUB-240729-2
- Date
- 2024
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 177: 117125117125 (Journal)
- Registered Authors
- Keywords
- Combination therapy, Drug targeting, Nanoparticles, Prostate specific membrane antigen, Reactive oxygen species
- MeSH Terms
-
- Animals
- Antigens, Surface*/metabolism
- Antineoplastic Agents/administration & dosage
- Antineoplastic Agents/pharmacology
- Cell Line, Tumor
- Docetaxel*/administration & dosage
- Docetaxel*/pharmacology
- Glutamate Carboxypeptidase II*/metabolism
- Humans
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Nanoparticle Drug Delivery System/chemistry
- Nanoparticles*/chemistry
- PC-3 Cells
- Prostatic Neoplasms*/drug therapy
- Prostatic Neoplasms*/pathology
- Reactive Oxygen Species/metabolism
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 39002444 Full text @ Biomed. Pharmacother.
Citation
Adekiya, T.A., Hudson, T., Bakare, O., Ameyaw, E.E., Adebayo, A., Olajubutu, O., Adesina, S.K. (2024) PSMA-targeted combination brusatol and docetaxel nanotherapeutics for the treatment of prostate cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 177:117125117125.
Abstract
Active targeting to cancer involves exploiting specific interactions between receptors on the surface of cancer cells and targeting moieties conjugated to the surface of vectors such that site-specific delivery is achieved. Prostate specific membrane antigen (PSMA) has proved to be an excellent target for active targeting to prostate cancer. We report the synthesis and use of a PSMA-specific ligand (Glu-NH-CO-NH-Lys) for the site-specific delivery of brusatol- and docetaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles to prostate cancer. The PSMA targeting ligand covalently linked to PLGA-PEG3400 was blended with methoxyPEG-PLGA to prepare brusatol- and docetaxel-loaded nanoparticles with different surface densities of the targeting ligand. Flow cytometry was used to evaluate the impact of different surface densities of the PSMA targeting ligand in LNCaP prostate cancer cells at 15 min and 2 h. Cytotoxicity evaluations of the targeted nanoparticles reveal differences based on PSMA expression in PC-3 and LNCaP cells. In addition, levels of reactive oxygen species (ROS) were measured using the fluorescent indicator, H2DCFDA, by flow cytometry. PSMA-targeted nanoparticles loaded with docetaxel and brusatol showed increased ROS generation in LNCaP cells compared to PC-3 at different time points. Furthermore, the targeted nanoparticles were evaluated in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors. Evaluation of the percent relative tumor volume show that brusatol-containing nanoparticles show great promise in inhibiting tumor growth. Our data also suggest that the dual drug-loaded targeted nanoparticle platform improves the efficacy of docetaxel in male athymic BALB/c mice implanted with PSMA-producing LNCaP cell tumors.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping