PSMA Antibody-Conjugated Pentablock Copolymer Nanomicellar Formulation for Targeted Delivery to Prostate Cancer
- 148 Downloads
The main purpose of this study was to develop a prostate-specific membrane antigen (PSMA) antibody-conjugated drug-loaded nanomicelles using MPEG--PLA-PCL-PLA-PEG-NH2 pentablock copolymer for targeted delivery of hydrophobic anticancer drugs to prostate cancer cells. During this experiment, monomers of L-lactide, ε-caprolactone, poly(ethylene glycol)-methyl ether, and poly(ethylene glycol)-NH2 were used to prepare pentablock copolymer using the ring opening technique. The pentablock nanomicellar (PBNM) formulation was prepared by the evaporation-rehydration method. The resultant pentablock nanomicelles were then conjugated with PSMA antibody resulting in PSMA-Ab-PTX-PBNM. Both the block copolymers and the nanomicelles were analyzed by hydrogen nuclear magnetic resonance (H-NMR), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The obtained nanomicelles (NM) were then analyzed for size and zeta potential using dynamic light scattering-dynamic laser scattering (DLS) and then further submitted to H-NMR and TEM analyses. The XRD, FTIR, and the H-NMR analyses confirmed the structure of the pentablock copolymers. The average size for conjugated nanomicellar was 45 nm ± 2.5 nm. The average (ζ-potential) was around − 28 mV. H-NMR and FTIR analysis done on PSMA-coupled paclitaxel-loaded PBNM showed peaks characteristic of the drug (paclitaxel) and the polymer, confirming the successful encapsulation. TEM analysis showed well-defined spherical morphology and confirmed the size range obtained by the DLS. In vitro release studies revealed sustained slow of PTX in phosphate buffer solution (PBS). Confocal scanning microscopy (TEM) of coumarin6-loaded in PBNM indicated that pentablock nanomicelles were internalized into the prostate cancer (PC-3) cells. Cell proliferation assay showed that nanomicelles ferried paclitaxel into the PC-3 cells and subsequently reduced the cell proliferation. The results depict PTX-PBNM-Ab as a suitable carrier for targeted delivery of drugs to prostate cancer cells.
KEY WORDSPSMA antibody prostate cancer pentablock copolymer nanomicelles paclitaxel targeted delivery
The authors would like to express the most sincere gratitude to: (1) CAPES Foundation, Ministry of Education of Brazil, Brasília - DF 70040-020, Brazil, for funding through SwB scholarship; (2) Ms. Barbara Fegley of the University of Kansas Medical Center for TEM facility; and (3) Mrs. Abrar Alnafisah for the FTIR facility.
- 3.Tamboli V, Mishra GP, Mitra AK. Novel pentablock copolymer (PLA-PCL-PEG-PCL-PLA) based nanoparticles for controlled drug delivery: effect of copolymer compositions on the crystallinity of copolymers and in vitro drug release profile from nanoparticles. Colloid Polym Sci. 2013;291(5):1235–45.CrossRefPubMedGoogle Scholar
- 6.Xia D, Lai DV, Wu W, Webb ZD, Yang Q, Zhao L, et al. Transition from androgenic to neurosteroidal action of 5alpha-androstane-3alpha, 17beta-diol through the type A gamma-aminobutyric acid receptor in prostate cancer progression. J Steroid Biochem Mol Biol 2017.Google Scholar
- 8.Chen Y, Su N, Zhang K, Zhu S, Zhao L, Fang F, et al. In-depth analysis of the structure and properties of two varieties of natural luffa sponge fibers. Materials. 2017;10(5).Google Scholar
- 32.Salgaller ML, Lodge PA, McLean JG, Tjoa BA, Loftus DJ, Ragde H, et al. Report of immune monitoring of prostate cancer patients undergoing T-cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen (PSMA). Prostate. 1998;35(2):144–51.CrossRefPubMedGoogle Scholar
- 33.Feldmann A, Arndt C, Bergmann R, Loff S, Cartellieri M, Bachmann D, et al. Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology “UniCAR”. Oncotarget. 2017;8(19):31368–85.CrossRefPubMedPubMedCentralGoogle Scholar