Journal of cellular physiology, 2020-05, Vol.235 (5), p.4618-4630
2020
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- Autor(en) / Beteiligte
- Titel
- PEG‐PLA nanoparticles decorated with small‐molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells
- Ist Teil von
- Journal of cellular physiology, 2020-05, Vol.235 (5), p.4618-4630
- Ort / Verlag
- United States: Wiley Subscription Services, Inc
- Erscheinungsjahr
- 2020
- Quelle
- Wiley Online Library Journals Frontfile Complete
- Beschreibungen/Notizen
- Prostate cancer (PCa) is one of the most prevalent non‐drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self‐assembled based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)‐2‐(3‐((S)‐5‐amino‐1‐carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate‐specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti‐proliferation of drugs‐loaded PEG‐PLA NPs and ACUPA‐PEG‐PLA against LNCaP (PSMA+) and PC3 (PSMA−) cells. PEG‐PLA NPs with an average size of 130–140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA‐modified PEG‐PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA‐conjugated PEG‐PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer‐targeting PSMA that suffer from short circulation half‐life and limited therapeutic efficacy. In this study, we report for the first time, a novel targeted self‐assembled drug delivery system based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ACUPA in prostate cancer cell line
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9541eISSN: 1097-4652DOI: 10.1002/jcp.29339Titel-ID: cdi_proquest_journals_2353495426
- Format
- –
- Schlagworte
- ACUPA, Antigens, Antigens, Surface - metabolism, Antineoplastic Combined Chemotherapy Protocols - chemistry, Antineoplastic Combined Chemotherapy Protocols - pharmacology, Cell Proliferation - drug effects, Cell Survival - drug effects, Coumarins - chemistry, Coumarins - metabolism, Coumarins - pharmacology, Cytotoxicity, docetaxel, Docetaxel - chemistry, Docetaxel - metabolism, Docetaxel - pharmacology, Drug Carriers, Drug Compounding, Drug delivery, Drug delivery systems, Drug Liberation, galbanic acid, Glutamate Carboxypeptidase II - metabolism, Glutarates - chemistry, Glutarates - metabolism, Humans, Ligands, Male, Nanoparticles, PC-3 Cells, pH effects, PLA nanoparticle, Polyethylene Glycols - chemistry, Prostate cancer, Prostatic Neoplasms - drug therapy, Prostatic Neoplasms - metabolism, Prostatic Neoplasms - pathology, Toxicity