PEG-PLA nanoparticles decorated with small-molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells.
J Cell Physiol
; 235(5): 4618-4630, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-31674023
ABSTRACT
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.
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1
Banco de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
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Neoplasias de la Próstata
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Portadores de Fármacos
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Protocolos de Quimioterapia Combinada Antineoplásica
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Cumarinas
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Glutamato Carboxipeptidasa II
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Nanopartículas
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Docetaxel
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Glutaratos
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Antígenos de Superficie
Límite:
Humans
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Male
Idioma:
En
Año:
2020
Tipo del documento:
Article